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Nuclear EGFR-PKM2 axis induces cancer stem cell-like characteristics in irradiation-resistant cells
Radiation therapy has become an important tool in the treatment of cancer patients, but most patients relapse within 5 years. Relapse is due to the presence of cancer stem cells (CSCs), but the molecular mechanism of radioresistance in CSCs remains largely elusive. Here, we found that irradiation-resistant (IR) cells exhibited increased stem cell-like properties together with elevated anchorage-independent growth and metastasis ability. EGFR not only leads to increased acquisition of endometrial cancer stem cell markers in radioresistant sublines but is critical for the cancer stem-cell phenotype and tumorigenicity. (Source: Cancer Letters)
Source: Cancer Letters - February 22, 2018 Category: Cancer & Oncology Authors: Ying Shi, Na Liu, Weiwei Lai, Bin Yan, Ling Chen, Shouping Liu, Shuang Liu, Xiang Wang, Desheng Xiao, Xiaoli Liu, Chao Mao, Yiqun Jiang, Jiantao Jia, Yating Liu, Rui Yang, Ya Cao, Yongguang Tao Tags: Original Articles Source Type: research

CD74-ROS1 G2032R mutation transcriptionally up-regulates Twist1 in non-small cell lung cancer cells leading to increased migration, invasion, and resistance to crizotinib
The c-ros oncogene 1 (ROS1) is a receptor tyrosine kinase, which has been identified as an oncogene driver of non-small-cell lung cancer (NSCLC). Although crizotinib has a prominent effect on ROS1, resistance is inevitable. Development of the acquired ROS1 G2032R mutation has been reported as a resistant mechanism to ROS1 inhibitors in ROS1-rearranged (ROS1+) NSCLC patients. To explore the mechanism of drug resistance, we constructed the crizotinib resistance cell line, A549-CD74-ROS1 G2032R mutation cells, by the methods of fusion polymerase chain reaction (PCR), plasmid construction and cell transfection in vitro. (Source: Cancer Letters)
Source: Cancer Letters - February 22, 2018 Category: Cancer & Oncology Authors: Wenfeng Gou, Xuejiao Zhou, Zi Liu, Lijing Wang, Jiwei Shen, Xiaobo Xu, Zengqiang Li, Xin Zhai, Daiying Zuo, Yingliang Wu Tags: Original Articles Source Type: research

Haploidentical IL-15/41BBL activated and expanded natural killer cell infusion therapy after salvage chemotherapy in children with relapsed and refractory leukemia
Primary refractory or relapsed pediatric leukemia yield significant morbidity and mortality, with long-term survival rates (Source: Cancer Letters)
Source: Cancer Letters - February 22, 2018 Category: Cancer & Oncology Authors: M. Vela, D. Corral, P. Carrasco, L. Fern ández, J. Valentín, B. González, A. Escudero, A. Balas, R. de Paz, J. Torres, A. Leivas, J. Martínez-López, A. Pérez-Martínez Tags: Original Articles Source Type: research

ICAM3 mediates inflammatory signaling to promote cancer cell stemness
In this study, we present a medium throughput siRNA screen platform to identify inflammation genes that regulate cancer cell stemness. We identified several novel candidates that decrease OCT4 expression and reduce the ALDH  + subpopulation both of which are characteristic of stemness. Furthermore, one of the novel candidates ICAM3 up-regulates in the ALDH + subpopulation, the side population and the developed spheres. ICAM3 knockdown reduces the side population, sphere formation and chemo-resistance in MDA-MB-231 human breast cancer cells and A549 lung cancer cells. (Source: Cancer Letters)
Source: Cancer Letters - February 22, 2018 Category: Cancer & Oncology Authors: Wenzhi Shen, Junling Xie, Shuangtao Zhao, Renle Du, Xiaohe Luo, Huiwen He, Shan Jiang, Na Hao, Chong Chen, Chunlei Guo, Yanhua Liu, Yanan Chen, Peiqing Sun, Shengyong Yang, Na Luo, Rong Xiang, Yunping Luo Tags: Original Articles Source Type: research

Oncogene-induced regulation of microRNA expression: Implications for cancer initiation, progression and therapy
A plethora of tumours have characteristic oncogenic mutations which are the main causes of malignant transformation, exerting their effects through multiple signalling pathways. Downstream of such pathways, microRNAs are small non-coding RNAs that negatively regulate gene expression, assisting or antagonizing oncogenic signalling. The differential expression of microRNAs in cancer is well-documented and is considered a fundamental aspect of tumourigenesis. While data mapping the interaction between oncogenic lesions and microRNAs are accruing, we provide particular cases of such interaction. (Source: Cancer Letters)
Source: Cancer Letters - February 21, 2018 Category: Cancer & Oncology Authors: Athanasios R. Paliouras, Tiziana Monteverde, Michela Garofalo Tags: Mini-review Source Type: research

An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis
Esophageal squamous cell carcinomas (ESCCs) have a poor prognosis mostly due to early metastasis. To explore the early event of metastasis in ESCC, we established an in vitro selection model to mimic the interaction of tumor cells with extracellular matrix, through which a sub-line of ESCC cells with high invasive ability was generated. By comparing the gene expression profile of the highly invasive sub-line to that of the parental cells, ADAM12-L was identified as a candidate gene promoting ESCC cell invasion. (Source: Cancer Letters)
Source: Cancer Letters - February 21, 2018 Category: Cancer & Oncology Authors: Man-Li Luo, Zhuan Zhou, Lichao Sun, Long Yu, Lixin Sun, Jun Liu, Zhihua Yang, Yuliang Ran, Yandan Yao, Hai Hu Tags: Original Articles Source Type: research

Molecular targets and anti-cancer potential of escin
Escin is a mixture of triterpenoid saponins extracted from the horse chestnut tree, Aesculus hippocastanum. Its potent anti-inflammatory and anti-odematous properties makes it a choice of therapy against chronic venous insufficiency and odema. More recently, escin is being actively investigated for its potential activity against diverse cancers. It exhibits anti-cancer effects in many cancer cell models including lung adenocarcinoma, hepatocellular carcinoma and leukemia. Escin also attenuates tumor growth and metastases in various in vivo models. (Source: Cancer Letters)
Source: Cancer Letters - February 20, 2018 Category: Cancer & Oncology Authors: Dorothy H.J. Cheong, Frank Arfuso, Gautam Sethi, Lingzhi Wang, Kam Man Hui, Alan Prem Kumar, Thai Tran Tags: Mini-review Source Type: research

Phytochemicals as potent modulators of autophagy for cancer therapy
The dysregulation of autophagy is involved in the pathogenesis of a broad range of diseases, and accordingly universal research efforts have focused on exploring novel compounds with autophagy-modulating properties. While a number of synthetic autophagy modulators have been identified as promising cancer therapy candidates, autophagy-modulating phytochemicals have also attracted attention as potential treatments with minimal side effects. In this review, we firstly highlight the importance of autophagy and its relevance in the pathogenesis and treatment of cancer. (Source: Cancer Letters)
Source: Cancer Letters - February 20, 2018 Category: Cancer & Oncology Authors: Mohammad Amin Moosavi, Atousa Haghi, Marveh Rahmati, Hiroaki Taniguchi, Andrei Mocan, Javier Echeverr ía, Vijai K. Gupta, Nikolay T. Tzvetkov, Atanas G. Atanasov Tags: Original Articles Source Type: research

Prostate cancer chemoprevention by natural agents: Clinical evidence and potential implications
Prostate cancer (PCa) is the most common non-skin cancer and the second leading cause of cancer-related deaths in American men. Due to its long latency period, PCa is considered as an ideal cancer type for chemopreventive interventions. Chemopreventive agents include various natural or synthetic agents that prevent or delay cancer development, progression and/or recurrence. Pre-clinical studies suggest that many natural products and dietary agents have chemopreventive properties. However, a limited number of these agents have been tested in clinical trials, with varying success. (Source: Cancer Letters)
Source: Cancer Letters - February 19, 2018 Category: Cancer & Oncology Authors: Gagan Chhabra, Chandra K. Singh, Mary Ann Ndiaye, Samantha Fedorowicz, Arielle Molot, Nihal Ahmad Tags: Mini-review Source Type: research

MiR-155-5p controls colon cancer cell migration via post-transcriptional regulation of Human Antigen R (HuR)
Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR. (Source: Cancer Letters)
Source: Cancer Letters - February 19, 2018 Category: Cancer & Oncology Authors: Amr Al-Haidari, Anwar Algaber, Raed Madhi, Ingvar Syk, Henrik Thorlacius Tags: Original Articles Source Type: research

The C/EBP β-LINC01133 axis promotes cell proliferation in pancreatic ductal adenocarcinoma through upregulation of CCNG1
In this study, we report that LINC01133 expression is higher in PDAC tissues compared to adjacent non-cancerous tissues, and this overexpression is associated with poorer prognosis among the patients. In vitro, a knockdown of LINC01133 substantially decreased PDAC cell proliferation. Tumorigenicity of PDAC cells with the LINC01133 knockdown was significantly impaired in a xenograft model assay. (Source: Cancer Letters)
Source: Cancer Letters - February 17, 2018 Category: Cancer & Oncology Authors: Chen-Song Huang, Junjun Chu, Xiao-Xu Zhu, Jian-Hui Li, Xi-Tai Huang, Jian-Peng Cai, Wei Zhao, Xiao-Yu Yin Tags: Original Articles Source Type: research

Disruption of peroxisome function leads to metabolic stress, mTOR inhibition, and lethality in liver cancer cells
Peroxisome houses a large number of enzymes involved in lipid and phytochemical oxidation as well as synthesis of bile acid and other specialized lipids. Peroxisome resident enzymes are imported into the organelle via a conserved cargo transport system composed of many peroxins, protein factors essential for the biogenesis of peroxisome. Among the peroxins, PEX5 plays a transporter role, and PEX2, 10, and 12 are thought to form a complex that functions as an E3 ubiquitin ligase to help recycle PEX5 in an ubiquitin modification-dependent process. (Source: Cancer Letters)
Source: Cancer Letters - February 17, 2018 Category: Cancer & Oncology Authors: Mengjiao Cai, Xiao Sun, Wenchao Wang, Zhusheng Lian, Ping Wu, Suxia Han, Huan Chen, Pumin Zhang Tags: Original Articles Source Type: research

Long non-coding RNAs within the tumour microenvironment and their role in tumour-stroma cross-talk
Long non-coding RNAs (lncRNAs) are a diverse class of RNA transcripts which have limited protein coding potential. They perform a variety of cellular functions in health, but have also been implicated during malignant transformation.A further theme in recent years is the critical role of the tumour microenvironment and the dynamic interactions between cancer and stromal cells in promoting invasion and disease progression. Whereas the contribution of deregulated lncRNAs within cancer cells has received considerable attention, their significance within the tumour microenvironment is less well understood. (Source: Cancer Letters)
Source: Cancer Letters - February 17, 2018 Category: Cancer & Oncology Authors: Filippo Del Vecchio, Gui Han Lee, Joamir Hawezi, Rahul Bhome, Sian Pugh, Emre Sayan, Gareth Thomas, Graham Packham, John Primrose, Martin Pichler, Alexander Mirnezami, George Calin, Marc Bullock Source Type: research

SUV39H2 promotes colorectal cancer proliferation and metastasis via tri-methylation of the SLIT1 promoter
Suppressor of variegation 3 –9 homolog 2 (SUV39H2) is a member of the SUV39H subfamily of lysine methyltransferases. Its role in colorectal cancer (CRC) proliferation and metastasis has remained unexplored. Here, we determined that SUV39H2 was upregulated in CRC tissues compared with that in adjacent non-neoplastic tissues. Further statistical analysis revealed that high SUV39H2 expression was strongly associated with distant metastasis (P = 0.016) and TNM stage (P = 0.038) and predicted a shorter overall survival (OS; P = 0.018) and progression-free survival (PFS; P = 0.018) time for CRC patients. (S...
Source: Cancer Letters - February 17, 2018 Category: Cancer & Oncology Authors: Wendi Shuai, Jiangxue Wu, Shuai Chen, Ranyi Liu, Zhihua Ye, Chunmei Kuang, Xiang Fu, Gaoyuan Wang, Yingchang Li, Qihua Peng, Wei Shi, Yizhuo Li, Qianghua Zhou, Wenlin Huang Tags: Original Articles Source Type: research

Insufficient radiofrequency ablation promotes proliferation of residual hepatocellular carcinoma via autophagy
Radiofrequency ablation (RFA) is considered to be a potentially curative therapy for hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can promote rapid progression of the residual tumor. The mechanisms underlying IRFA-induced tumor promotion remain poorly understood. In the present study, we have established a subcutaneous xenograft mouse model and monitored the location and extent of IRFA by dual monitoring with ultrasonography and a thermal imager. For the first time, we provide evidence of the activation of autophagic pathways in mice exposed to IRFA. (Source: Cancer Letters)
Source: Cancer Letters - February 17, 2018 Category: Cancer & Oncology Authors: Zizhuo Zhao, Jiayi Wu, Xiaodi Liu, Ming Liang, Xinchuan Zhou, Shi Ouyang, Jiyi Yao, Jinquan Wang, Baoming Luo Tags: Original Articles Source Type: research

Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - February 16, 2018 Category: Cancer & Oncology Source Type: research

Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression
In this study, high throughput microarray assay revealed that hsa_circ_0000977 was aberrantly up-regulated in pancreatic cancer tissues; this was also validated by qRT-PCR. (Source: Cancer Letters)
Source: Cancer Letters - February 15, 2018 Category: Cancer & Oncology Authors: Wen-Jie Huang, Yun-Chao Wang, Song-Song Liu, Jia-Li Yang, Shi-Xiang Guo, Li-Jiang Wang, Huai-Zhi Wang, Ying-Fang Fan Tags: Original Articles Source Type: research

Synergistic activity of BET inhibitor BI 894999 with PLK inhibitor volasertib in AML in vitro and in vivo
Interactions between a new potent Bromodomain and extraterminal domain (BET) inhibitor BI 894999 and the polo-like kinase (PLK) inhibitor volasertib were studied in acute myeloid leukemia cell lines in vitro and in vivo. We provide data for the distinct mechanisms of action of these two compounds with a potential utility in AML based on gene expression, cell cycle profile and modulation of PD biomarkers such as MYC and HEXIM1. In contrast to BI 894999, volasertib treatment neither affects MYC nor HEXIM1 expression, but augments and prolongs the decrease of MYC expression caused by BI 894999 treatment. (Source: Cancer Letters)
Source: Cancer Letters - February 15, 2018 Category: Cancer & Oncology Authors: Ulrike Tontsch-Grunt, Dorothea Rudolph, Irene Waizenegger, Anke Baum, Daniel Gerlach, Harald Engelhardt, Melanie Wurm, Fabio Savarese, Norbert Schweifer, Norbert Kraut Tags: Original Articles Source Type: research

An esophageal adenocarcinoma susceptibility locus at 9q22 also confers risk to esophageal squamous cell carcinoma by regulating the function of BARX1
Genome wide association studies (GWAS) have identified a series of genetic variants associated with the risk of esophageal adenocarcinoma (EAC)/Barrett's esophagus (BE), which was different from those loci for esophageal squamous cell carcinoma (ESCC). It is important to evaluate whether these susceptibility loci for EAC/BE are also implicated in ESCC development. In the current study, we analyzed genetic variants at 3p13, 9q22, 16q24 and 19p13 in a case-control study including 2139 ESCC patients and 2463 cancer-free controls in a Chinese population, and further characterized the biological relevance of genetic variants by...
Source: Cancer Letters - February 15, 2018 Category: Cancer & Oncology Authors: Caiwang Yan, Yong Ji, Tongtong Huang, Fei Yu, Yong Gao, Yayun Gu, Qi Qi, Jiangbo Du, Juncheng Dai, Hongxia Ma, Guangfu Jin Tags: Original Articles Source Type: research

RNA biology-featuring the special issue guest editors “cancer letters”
Girish C. Shukla earned his Ph.D. degree at the Brunel University, London, UK. His Ph.D. research was involved in regulation of fragmented mitochondrial ribosomal RNAs of protozoan parasite at International Livestock Research Institute, Nairobi, Kenya and in Brunel University, London, UK. After, Ph.D. Dr. Shukla joined the laboratory of Dr. Richard A. Padgett, in Molecular Genetics, Lerner Research Institute, Cleveland Clinic, OH, USA, as a postdoctoral fellow. While working in Dr. Padgett laboratory, he demonstrated that the group II domain V could function in the human spliceosome. (Source: Cancer Letters)
Source: Cancer Letters - February 13, 2018 Category: Cancer & Oncology Authors: Girish C. Shukla, Sanjay Gupta Source Type: research

Recent progress in immune-metabolism
The field of immune-metabolism has recently drawn a great deal of attention. Over the last decade, researchers have made substantial progress in elucidating how various immune cell subtypes modulate their functional roles through regulation of cellular metabolism. The immune system comprises a heterogeneous population of various subtypes of immune cells that are quiescent in their naive state, and that can rapidly respond to external interruptions, such as pathogen infections or antigen challenges. (Source: Cancer Letters)
Source: Cancer Letters - February 13, 2018 Category: Cancer & Oncology Authors: Shuai Jiang Tags: Special Issue Editorial Source Type: research

The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer
The Hippo pathway plays a critical role in organ size control, tissue homeostasis and tumor genesis through its key transcription regulator Yes-associated protein1 (YAP1), but the mechanism underlying its role in lung cancer is unclear. We hypothesized that YAP1 influences FGFR1 signaling to maintain cancer stem-like cell (CSC) properties in FGFR1-amplified lung cancer. In support of this, our data confirms that expression levels of YAP1 are positively associated with those of FGFR1 in clinical lung carcinoma samples as measured by real-time PCR, western blot, and immunohistochemistry (IHC) staining. (Source: Cancer Letters)
Source: Cancer Letters - February 13, 2018 Category: Cancer & Oncology Authors: Tingting Lu, Ziming Li, Ying Yang, Wenxiang Ji, Yongfeng Yu, Xiaomin Niu, Qingyu Zeng, Weiliang Xia, Shun Lu Tags: Original Articles Source Type: research

Combination of Kras activation and PTEN deletion contributes to murine hepatopancreatic ductal malignancy
Kras mutations are among the most common genetic abnormalities in human neoplasms, including cholangiocarcinomas, pancreatic cancer and colon cancer. PTEN has previously been associated with cholangiocarcinoma development in murine models. Here, we have established novel mouse models of neoplasms by liver-specific and biliary-pancreatic Kras activation and PTEN deletion. By liver-specific disruption of PTEN and activation of Kras in mice caused rapid development of intrahepatic biliary epithelial proliferative lesions (Intrahepatic cholangiocarcinoma, ICC), which progress through dysplasia to invasive carcinoma. (Source: Cancer Letters)
Source: Cancer Letters - February 13, 2018 Category: Cancer & Oncology Authors: Yun-kai Lin, Zheng Fang, Tian-yi Jiang, Zheng-hua Wan, Yu-fei Pan, Yun-han Ma, Yuan-yuan Shi, Ye-xiong Tan, Li-wei Dong, Yong-jie Zhang, Hong-yang Wang Tags: Original Articles Source Type: research

Bone marrow-derived fibrocytes promote stem cell-like properties of lung cancer cells
Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact. Fibrocytes are differentiated from bone marrow-derived CD14+ monocytes and have features of both macrophages and fibroblasts. (Source: Cancer Letters)
Source: Cancer Letters - February 12, 2018 Category: Cancer & Oncology Authors: Atsuro Saijo, Hisatsugu Goto, Mayuri Nakano, Atsushi Mitsuhashi, Yoshinori Aono, Masaki Hanibuchi, Hirohisa Ogawa, Hisanori Uehara, Kazuya Kondo, Yasuhiko Nishioka Tags: Original Articles Source Type: research

ADAM9 mediates the interleukin-6-induced Epithelial –Mesenchymal transition and metastasis through ROS production in hepatoma cells
Interleukin (IL)-6 has been implicated in the invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular events that mediate this process are poorly understood. Here, we showed that IL-6 promoted the epithelial –mesenchymal transition (EMT) in HCC cell lines, and upregulated a disintegrin and metalloprotease 9 (ADAM9) expression by activating the JNK signaling pathway. ADAM9 was upregulated in human HCCs which promoted HCC cell invasion and the EMT by interacting with NADPH oxidase 1 and inducing reactiv e oxygen species generation. (Source: Cancer Letters)
Source: Cancer Letters - February 9, 2018 Category: Cancer & Oncology Authors: Yinying Dong, Zhifeng Wu, Mingyan He, Yuhan Chen, Yixing Chen, Xiaoyun Shen, Xiaomei Zhao, Li Zhang, Baoying Yuan, Zhaochong Zeng Tags: Original Articles Source Type: research

NF- κB in pancreatic cancer: Its Key Role in Chemoresistance
Pancreatic cancer is considered a lethal disease with a high mortality and an extremely low five-year survival rate. Chemotherapy plays a pivotal role in pancreatic cancer treatment both in an adjuvant setting after complete resection and in the case of unresectable metastatic disease. However, none of the available combination chemotherapy regimens has resulted in satisfactory survival outcomes. Recent studies have revealed that both constitutive and induced activation of nuclear factor kappa B (NF- κB) in pancreatic cancer cells are closely associated with cell proliferation, invasion, anti-apoptosis, inflammation,...
Source: Cancer Letters - February 9, 2018 Category: Cancer & Oncology Authors: Quanxiao Li, Gang Yang, Mengyu Feng, Suli Zheng, Zhe Cao, Jiangdong Qiu, Lei You, Lianfang Zheng, Ya Hu, Taiping Zhang, Yupei Zhao Tags: Mini-review Source Type: research

Pharmacogenomics signature: A novel strategy on the individual differences in drug response
Patients exhibit a wide heterogeneity in their responses to a drug treatment due to variations in the molecular determinants underlying this heterogeneity. Pharmacogenomics approaches can be used to integrate information on drug responsiveness with alterations in molecular entities, often on a genome-wide scale. However, most of the studies involving pharmacogenomics of specific therapeutics are in their early stages and thus are not ready for clinical utilization. Genotyping studies tackle around a candidate gene approach using genes known to be important in the pharmacokinetics and pharmacodynamics of the administered dr...
Source: Cancer Letters - February 9, 2018 Category: Cancer & Oncology Authors: Chengxian Guo, Xinjian Lin, Jiye Yin, Xiaoxue Xie, Jingao Li, Xiangguang Meng, Jichu Wu, Lihua Huang, Zhijun Huang, Guoping Yang, Honghao Zhou, Xiang Chen Tags: Mini-review Source Type: research

Ascitic fluid from advanced ovarian cancer patients compromises the activity of receptor tyrosine kinase inhibitors in 3D cell clusters of ovarian cancer cells
Ovarian cancer patients in the advanced stages of the disease show clinical ascites, which is associated with a poor prognosis. There is limited understanding of the effect of ascitic fluid on ovarian cancer cells and their response to anticancer drugs. We investigated the antitumour effects of EGFR/Her-2 (canertinib) and c-Met (PHA665752) inhibitors in a 3D cell model of three ovarian cancer lines. Single and combined inhibitor treatments affected cell growth of OVCAR-5 and SKOV-3  cell lines but not OV-90 cell line. (Source: Cancer Letters)
Source: Cancer Letters - February 9, 2018 Category: Cancer & Oncology Authors: Wafaa Hassan, Kenny Chitcholtan, Peter Sykes, Ashley Garrill Tags: Original Articles Source Type: research

Corrigendum to “MiR-590-5p, a density-sensitive microRNA, inhibits tumorigenesis by targeting YAP1 in colorectal cancer”, [Canc. Lett. 399 (2017) 53–63]
The authors regret that the “Acknowledgement” section for this article was not included due to their carelessness. The authors would like to add an “Acknowledgement” section to this article as below: (Source: Cancer Letters)
Source: Cancer Letters - February 8, 2018 Category: Cancer & Oncology Authors: Chunlin Ou, Zhenqiang Sun, Xiayu Li, Xiaoling Li, Weiguo Ren, Zailong Qin, Xuemei Zhang, Weitang Yuan, Jia Wang, Wentao Yu, Shiwen Zhang, Qiu Peng, Qun Yan, Wei Xiong, Guiyuan Li, Jian Ma Tags: Corrigendum Source Type: research

Dual inhibition of mTORC1/2 by DCZ0358 induces cytotoxicity in multiple myeloma and overcomes the protective effect of the bone marrow microenvironment
Interaction of multiple myeloma (MM) cells with the bone marrow (BM) microenvironment promotes the proliferation, survival and chemoresistance of MM. The mTOR pathway plays a key role in these undesirable BM microenvironment-mediated events. We synthesized a novel alkaloid compound, DCZ0358, that effectively inhibits mTOR signaling via dual mTORC1/2 inhibition and exhibits potent anti-MM activity in cultured and primary MM cells, as well as a MM xenograft model but has little effect on normal cells. (Source: Cancer Letters)
Source: Cancer Letters - February 8, 2018 Category: Cancer & Oncology Authors: Lu Gao, Bo Li, Guang Yang, Peng Liu, Xiucai Lan, Shuaikang Chang, Yi Tao, Zhijian Xu, Bingqian Xie, Xi Sun, Yingcong Wang, Liangning Hu, Dandan Yu, Yongsheng Xie, Wenxuan Bu, Xiaosong Wu, Weiliang Zhu, Jumei Shi Tags: Original Articles Source Type: research

Crucial role of non-coding RNAs in disease
Non-coding RNAs (ncRNAs) are RNA molecules with no/limited protein coding capacity. They are major components among total RNAs in human cells and were initially thought as non-functional junk RNA, ignored for a long time. During the last decades, owing to the improvement of sequencing technology and bioinformatics analysis, more and more ncRNAs with important biological function have been characterized and identified in different organisms. Increasing evidences show that ncRNAs play important roles in physiological and pathological processes, so ncRNAs are widely involved in human diseases, such as cancer, metabolism disor...
Source: Cancer Letters - February 6, 2018 Category: Cancer & Oncology Authors: Yong Peng, George A. Calin Tags: Editorial Source Type: research

Exosomal microRNAs (exomiRs): Small molecules with a big role in cancer
Exosomes are secreted vesicles which can transmit molecular cargo between cells. Exosomal microRNAs (exomiRs) have drawn much attention in recent years because there is increasing evidence to suggest that loading of microRNAs into exosomes is not a random process. Preclinical studies have identified functional roles for exomiRs in influencing many hallmarks of cancer. Mechanisms underpinning these actions, such as exomiR receptors ( “miRceptors”), are now becoming apparent. Even more exciting is the fact that exomiRs are highly suitable candidates for use as non-invasive biomarkers in an era of personalized can...
Source: Cancer Letters - February 6, 2018 Category: Cancer & Oncology Authors: Rahul Bhome, Filippo Del Vecchio, Gui-Han Lee, Marc D. Bullock, John N. Primrose, A. Emre Sayan, Alex H. Mirnezami Source Type: research

Out of the darkness and into the light: New strategies for improving treatments for locally advanced non-small cell lung cancer
The standard treatment for locally advanced non-small cell lung cancer (LA NSCLC) includes surgery, radiotherapy, chemotherapy, or some combination of these modalities. Many clinical trials have been conducted in attempts to intensify treatment for LA NSCLC, but with little improvement. A therapeutic plateau had been reached, with no major progress in extending survival for patients with this disease. However, several recent trials of newer targeted therapies and immunotherapies may shed new light on potential therapeutic breakthroughs. (Source: Cancer Letters)
Source: Cancer Letters - February 6, 2018 Category: Cancer & Oncology Authors: Yun Zhang, Qin Lin, Ting Xu, Weiye Deng, Jinming Yu, Zhongxing Liao, Jinbo Yue Tags: Mini-review Source Type: research

Osimertinib resistance in non-small cell lung cancer: Mechanisms and therapeutic strategies
Given the successful identification of epidermal growth factor receptor EGFR T790M, the third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib (OSI, AZD9291), was developed to target EGFR T790M mutation. OSI was approved for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR T790M mutation. However, the disease would progress after the patient received OSI treatment for approximately 10 months. Resistance mechanisms to OSI, such as additional mutation of EGFR and alternative kinase activation, were recently identified, and some novel therapeutic strategies were proposed to overcome...
Source: Cancer Letters - February 6, 2018 Category: Cancer & Oncology Authors: Zheng-Hai Tang, Jin-Jian Lu Tags: Mini-review Source Type: research

Cynanbungeigenin C and D, a pair of novel epimers from Cynanchum bungei, suppress hedgehog pathway-dependent medulloblastoma by blocking signaling at the level of Gli
Uncontrolled excessive activation of Hedgehog (Hh) signaling pathway is linked to a number of human malignant tumorigenesis. To obtain valuable Hh pathway inhibitors from natural product, in present study, a pair of novel epimers, Cynanbungeigenin C (CBC) and D (CBD) from the plant Cynanchum bungei Decne were chemically characterized by multiple spectroscopic data and chemical derivatization, and evaluated for their inhibition on Hh pathway. Mechanistically, CBC and CBD block Hh pathway signaling not through targeting Smo and Sufu, but at the level of Gli. (Source: Cancer Letters)
Source: Cancer Letters - February 6, 2018 Category: Cancer & Oncology Authors: Xiao-Yu Li, Li-Fei Zhou, Li-Juan Gao, Yang Wei, Shi-Fang Xu, Feng-Yang Chen, Wen-Jing Huang, Wen-Fu Tan, Yi-Ping Ye Tags: Original Articles Source Type: research

Novel ex vivo ovarian cancer tissue explant assay for prediction of chemosensitivity and response to novel therapeutics
The majority of ovarian cancer patients present with advanced disease and despite aggressive treatment, prognosis remains poor. Response to first-line carboplatin-containing chemotherapy is usually good, however, recurrence rates and subsequent chemoresistance are very high and ultimately responsible for the fatal outcome of the disease. To improve treatment outcomes pre-clinical models that can predict individual patient response to 1st line chemotherapy and novel therapeutics are urgently required. (Source: Cancer Letters)
Source: Cancer Letters - February 6, 2018 Category: Cancer & Oncology Authors: Carmela Ricciardelli, Noor A. Lokman, Ilhamjan Sabit, Kavyadharshini Gunasegaran, Wendy M. Bonner, Carmen E. Pyragius, Anne M. Macpherson, Martin K. Oehler Source Type: research

ASC-J9 ® suppresses prostate cancer cell invasion via altering the sumoylation-phosphorylation of STAT3
Unlike the androgen-deprivation therapy (ADT) to either reduce the androgen biosynthesis (for example, Abiraterone) or to prevent binding of androgen to the androgen receptor (AR) (for example, Casodex or Enzalutamide), that may result in the decreasing the prostate cancer (PCa) cell growth yet may also increasing the PCa cell invasion, the recently identified AR degradation enhancer ASC-J9 ® may function via degrading the AR protein to simultaneously suppress the PCa cell proliferation and invasion. (Source: Cancer Letters)
Source: Cancer Letters - February 6, 2018 Category: Cancer & Oncology Authors: WanYing Lin, Jie Luo, Yin Sun, ChangYi Lin, Gonghui Li, Yuanjie Niu, Chawnshang Chang Tags: Original Articles Source Type: research

Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - February 5, 2018 Category: Cancer & Oncology Source Type: research

Nuclear translocation of IGF1R by intracellular amphiregulin contributes to the resistance of lung tumour cells to EGFR-TKI
Many Receptor Tyrosine Kinases translocate from the cell surface to the nucleus in normal and pathological conditions, including cancer. Here we report the nuclear expression of insulin-like growth factor-1 receptor (IGF1R) in primary human lung tumours. Using lung cancer cell lines and lung tumour xenografts, we demonstrate that the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib induces the nuclear accumulation of IGF1R in mucinous lung adenocarcinoma by a mechanism involving the intracellular re-localization of the growth factor amphiregulin. (Source: Cancer Letters)
Source: Cancer Letters - February 5, 2018 Category: Cancer & Oncology Authors: Marie Guerard, Thomas Robin, Pascal Perron, Anne-Sophie Hatat, Laurence David-Boudet, Laetitia Vanwonterghem, Benoit Busser, Jean-Luc Coll, Sylvie Lantuejoul, Beatrice Eymin, Amandine Hurbin, Sylvie Gazzeri Tags: Original Articles Source Type: research

Smac mimetic induces an early wave of gene expression via NF- κB and AP-1 and a second wave via TNFR1 signaling
In this study, we used an unbiased genome-wide expression array to investigate gene regulation induced by the Smac mimetic BV6 in breast cancer cell lines. Here, we discover that tumor necrosis factor (TNF) α/TNF receptor 1 (TNFR1) auto-/paracrine signaling regulates Smac mimetic-stimulated changes in gene expression in a time-dependent manner. (Source: Cancer Letters)
Source: Cancer Letters - February 5, 2018 Category: Cancer & Oncology Authors: Nadine Schmidt, Tinka Haydn, Ines Schneider, Hauke Busch, Melanie Boerries, Simone Fulda Tags: Original Articles Source Type: research

Cortactin recruits FMNL2 to promote actin polymerization and endosome motility in invadopodia formation
Recently, invadopodia have been increasingly recognized as important drivers of local invasion and metastasis. Cortactin, as an actin-binding protein, is closely associated with invadopodia through interacting with proteins. Formin-like 2 (FMNL2), a member of diaphanous-related formins which act as nucleation factors, plays an important role in tumor progression. But whether cortactin can interact with FMNL2 to promote invadopodia formation and the role of FMNL2 in invadopodia formation are still unknown. (Source: Cancer Letters)
Source: Cancer Letters - February 4, 2018 Category: Cancer & Oncology Authors: X.L. Ren, Y.D. Qiao, J.Y. Li, X.M. Li, D. Zhang, X.J. Zhang, X.H. Zhu, W.J. Zhou, J. Shi, W. Wang, W.T. Liao, Y.Q. Ding, L. Liang Tags: Original Articles Source Type: research

BAFfling pathologies: Alterations of BAF complexes in cancer
To activate or repress specific genes, chromatin is constantly modified by chromatin-remodeling complexes. Among these complexes, the SWItch/Sucrose Non-Fermenting (SWI/SNF) complex, also referred to as BRG1-Associated Factor (BAF) complex, moves the nucleosome along chromatin using energy provided by ATP hydrolysis. In mammalian organisms, the SWI/SNF complex is composed of 10 –15 subunits, depending on cell type, and a defect in one of these subunits can have dramatic consequences. In this review we will focus on the alterations identified in the SWI/SNF (BAF) complex subunits that lead to cancerous pathologies. (S...
Source: Cancer Letters - February 4, 2018 Category: Cancer & Oncology Authors: Ophelie Arnaud, Fran çois Le Loarer, Franck Tirode Tags: Mini-review Source Type: research

Repurposing psychiatric drugs as anti-cancer agents
Cancer is a major public health problem and one of the leading contributors to the global disease burden. The high cost of development of new drugs and the increasingly severe burden of cancer globally have led to increased interest in the search and development of novel, affordable anti-neoplastic medications. Antipsychotic drugs have a long history of clinical use and tolerable safety; they have been used as good targets for drug repurposing. Being used for various psychiatric diseases for decades, antipsychotic drugs are now reported to have potent anti-cancer properties against a wide variety of malignancies in additio...
Source: Cancer Letters - February 4, 2018 Category: Cancer & Oncology Authors: Jing Huang, Danwei Zhao, Zhixiong Liu, Fangkun Liu Tags: Mini-review Source Type: research

Inhibition of dipeptidyl peptidase IV prevents high fat diet-induced liver cancer angiogenesis by downregulating chemokine ligand 2
Obesity is a major risk factor for hepatocellular carcinoma (HCC) and is typically accompanied by higher levels of serum dipeptidyl peptidase 4 (DPP4). However, the role of DPP4 in obesity-promoted HCC is unclear. Here, we found that consumption of a high-fat diet (HFD) promoted HCC cell proliferation and metastasis and led to poor survival in a carcinogen-induced model of HCC in rats. Notably, genetic ablation of DPP4 or treatment with a DPP4 inhibitor (vildagliptin) prevented HFD-induced HCC. Moreover, HFD-induced DPP4 activity facilitated angiogenesis and cancer cell metastasis in vitro and in vivo, and vildagliptin pre...
Source: Cancer Letters - February 4, 2018 Category: Cancer & Oncology Authors: Chen-Jie Qin, Ling-Hao Zhao, Xu Zhou, Hui-Lu Zhang, Wen Wen, Liang Tang, Min Zeng, Ming-Da Wang, Gong-Bo Fu, Shuai Huang, Wei-Jian Huang, Yuan Yang, Zhi-Jun Bao, Wei-Ping Zhou, Hong-Yang Wang, He-Xin Yan Tags: Original Articles Source Type: research

Survivin-targeting miR-542-3p overcomes HER3 signaling-induced chemoresistance and enhances the antitumor activity of paclitaxel against HER2-overexpressing breast cancer
Elevated expression of HER3, which interacts with HER2 in breast cancer cells, confers chemoresistance via phosphoinositide 3-kinase (PI-3K)/Akt-dependent upregulation of Survivin. However, the underlying mechanism is not clear. Ectopic expression or specific knockdown of HER3 in HER2-overexpressing breast cancer cells did not alter Survivin mRNA levels and Survivin protein stability, supporting the notion that HER3 signaling may regulate specific miRNAs that target Survivin to alter its protein translation. (Source: Cancer Letters)
Source: Cancer Letters - February 4, 2018 Category: Cancer & Oncology Authors: Hui Lyu, Shuiliang Wang, Jingcao Huang, Bolun Wang, Zhimin He, Bolin Liu Tags: Original Articles Source Type: research

Novel carbazole sulfonamide microtubule-destabilizing agents exert potent antitumor activity against esophageal squamous cell carcinoma
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide due to its chemoresistance and poor prognosis. Currently, there is a lack of effective small molecule drugs for the treatment of ESCC. Microtubules are an attractive target for cancer therapy since they play a central role in various fundamental cell functions. We investigated the anti-ESCC activity and mechanisms of the small molecule tubulin ligands, SL-3-19 and SL-1-73, which are two carbazole sulfonamide derivatives, in vitro and in vivo for the first time. (Source: Cancer Letters)
Source: Cancer Letters - February 4, 2018 Category: Cancer & Oncology Authors: Fangfei Niu, Yonghua Liu, Zongpan Jing, Gaijing Han, Lianqi Sun, Lu Yan, Lanping Zhou, Yanbin Wu, Yang Xu, Laixing Hu, Xiaohang Zhao Tags: Original Articles Source Type: research

LZTS2 inhibits PI3K/AKT activation and radioresistance in nasopharyngeal carcinoma by interacting with p85
Phosphoinositide 3-kinase (PI3K) activity is aberrantly activated in nasopharyngeal carcinoma. However, the underlying mechanisms remain unclear. Here, we found that Leucine zipper tumor suppressor 2 (LZTS2) was downregulated and predicted poor prognosis in nasopharyngeal carcinoma patients. Furthermore, we identified the PI3K subunit p85 as a novel LZTS2-interacting protein using an unbiased proteomics approach. Moreover, we demonstrated that LZTS2 competes with p110 for p85 binding and inhibits activation of the PI3K/AKT signaling pathway. (Source: Cancer Letters)
Source: Cancer Letters - February 4, 2018 Category: Cancer & Oncology Authors: Shuangbing Xu, Yan Li, Yanwei Lu, Jing Huang, Jinghua Ren, Sheng Zhang, Zhongyuan Yin, Kai Huang, Gang Wu, Kunyu Yang Tags: Original Articles Source Type: research

Non-apoptotic Cell Death in Malignant Tumor Cells and Natural Compounds
Traditional cancer therapy is mainly targeting on enhancing cell apoptosis, however, it is well established that many cancer cells are chemo-resistant and defective in apoptosis induction. Therefore, it may have important therapeutic implications to exploit some novel natural compounds based on non-apoptotic programmed cell death. Currently, accumulating evidence shows that the compounds from nature source can induce non-apoptotic programmed cell death in cancer cells, and therefore these natural compounds have gained a great promise for the future anticancer therapeutics. (Source: Cancer Letters)
Source: Cancer Letters - February 3, 2018 Category: Cancer & Oncology Authors: Jing Ye, Ruonan Zhang, Fan Wu, Lijuan Zhai, Kaifeng Wang, Mang Xiao, Tian Xie, Xinbing Sui Tags: Mini-review Source Type: research

Histone deacetylase inhibitors upregulate Snail via Smad2/3 phosphorylation and stabilization of Snail to promote metastasis of hepatoma cells
Hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related mortality. Resection and transplantation are the only curative treatments available, but are greatly hampered by high recurrence rates. Histone deacetylase inhibitors (HDACIs) are considered to be promising anticancer agents in drug development. Currently, four HDACIs have been granted Food and Drug Administration (FDA) approval for cancer. HDACIs have shown significant efficacy in hematological malignancies. However, they have limited effects in epithelial cell-derived cancers, including HCC, and the mechanisms of these are not elucidated...
Source: Cancer Letters - February 3, 2018 Category: Cancer & Oncology Authors: Wei Xu, Hao Liu, Zhi-Gang Liu, Hong-Sheng Wang, Fan Zhang, Hao Wang, Ji Zhang, Jing-Jing Chen, Hong-Jun Huang, Yuan Tan, Meng-Ting Cao, Jun Du, Qiu-Gui Zhang, Guan-Min Jiang Tags: Original Articles Source Type: research

Combined inhibition of PI3K δ and FLT3 signaling exerts synergistic antitumor activity and overcomes acquired drug resistance in FLT3-activated acute myeloid leukemia
In this report, we demonstrate that combined inhibition of PI3Kδ and FLT3 exerts synergistic antitumor activity in FLT3-activated AML. Synergistic antiproliferative effect s were observed in FLT3-activated MV-4-11 and EOL-1 AML cell lines, but not in FLT3-independent RS4;11 and HEL cells, as demonstrated by both pharmacological inhibition and silencing of PI3Kδ/FLT3. Combined treatment with PI3Kδ and FLT3 inhibitors more effectively inhibited AKT and ERK phosphoryla tion, and induced apoptosis more efficiently than either agent alone. (Source: Cancer Letters)
Source: Cancer Letters - February 3, 2018 Category: Cancer & Oncology Authors: Ye He, Liping Sun, Yongping Xu, Li Fu, Yun Li, Xubin Bao, Haoyu Fu, Chengying Xie, Liguang Lou Tags: Original Articles Source Type: research