Polo-like kinase 1 inhibitor BI 6727 induces DNA damage and exerts strong antitumor activity in small cell lung cancer
The prognosis of small cell lung cancer (SCLC) is poor despite its good initial response to chemotherapy. Polo-like kinase 1 (PLK1) is a crucial mitotic regulator that is overexpressed in many tumors, and its overexpression is associated with tumor aggressiveness and a poor prognosis. However, its role in SCLC is still poorly characterized. Based on immunohistochemistry findings, the PLK1 protein is expressed at higher levels in SCLC tumor samples than in normal lung tissue samples. The selective PLK1 inhibitor BI 6727 significantly induced the inhibition of proliferation and apoptosis in a dose-dependent manner in SCLC ce...
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Yuehong Wang, Linying Wu, Yinan Yao, Guohua Lu, Liming Xu, Jianying Zhou Tags: Original Articles Source Type: research

Designer hydrogels: Shedding light on the physical chemistry of the pancreatic cancer microenvironment
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality in the United States, with a 5-year survival of ∼8%. PDAC is characterized by a dense and hypo-vascularized stroma consisting of proliferating cancer cells, cancer-associated fibroblasts, macrophages and immune cells, as well as excess matrices including collagens, fibronectin, and hyaluronic acid. In addition, PDAC has increased interstitial p ressures and a hypoxic/acidic tumor microenvironment (TME) that impedes drug delivery and blocks cancer-directed immune mechanisms. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Chien-Chi Lin, Murray Korc Tags: Mini-review Source Type: research

TGF- β-induced STAT3 overexpression promotes human head and neck squamous cell carcinoma invasion and metastasis through malat1/miR-30a interactions
Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is a critical factor that drives the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of STAT3 overexpression and regulation of HNSCC metastasis remain unknown. In the current study, we demonstrated that upregulated TGF- β may promote epithelial-mesenchymal transition (EMT) through STAT3 activation. In addition, we explored the contributions of STAT3 to HNSCC with a specific focus on its transcriptional regulation and its interaction with the long noncoding RNA (lncRNA) metastasis a...
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Yu Wang, Chuanqiang Wu, Chao Zhang, Zhaoqing Li, Tingting Zhu, Jinliang Chen, Yu Ren, Xudong Wang, Lun Zhang, Xuan Zhou Tags: Original Articles Source Type: research

USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by inhibiting autophagy
Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective in most patients, development of tumor resistance to gemcitabine can critically limit its efficacy. The mechanisms responsible for this phenomenon remain elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be key regulators in cancer chemo-resistance. The present study aimed to investigate the role of USP9X in gemcitabine resistance using in vitro pancreatic cell lines and a mouse xenograft model. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Tao Ma, Wei Chen, Xiao Zhi, Hao Liu, Yue Zhou, Brayant Wei Chen, Liqiang Hu, Jian Shen, Xiaoxiao Zheng, Shufen Zhang, Tingbo Liang Tags: Original Articles Source Type: research

PTEN deficiency confers colorectal cancer cell resistance to dual inhibitors of FLT3 and aurora kinase A
PTEN is a tumor suppressor found mutated in many cancers. From a synthetic lethality drug screen with PTEN-isogenic colorectal cancer cells, we found that mutant-PTEN cells were resistant to dual inhibitors of FLT3 and aurora kinase-A, including KW2449 and ENMD-2076. KW2449 significantly reduced the viability of wildtype-PTEN cells causing apoptosis, while little effect was observed in mutant-PTEN counterparts. Transcriptome profiling showed that members of PI3K-AKT signaling pathway were strongly changed in cells after KW2449 treatment, indicating a potential role of the pathway in drug resistance. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Yifan Liu, Eun Ju Yang, Baoyuan Zhang, Zhengqiang Miao, Changjie Wu, Junfang Lyu, Kaeling Tan, Terence Chuen Wai Poon, Joong Sup Shim Tags: Original Articles Source Type: research

Tim-4 promotes the growth of colorectal cancer by activating angiogenesis and recruiting tumor-associated macrophages via the PI3K/AKT/mTOR signaling pathway
In this study, we investigated the physiological alterations and molecular events related to Tim-4 overexpression in a mouse model of colorectal cancer (CRC). In the current study, we observed that Tim-4 is upregulated in CRC tissues compared with neighboring normal tissues. In addition, statistical analysis revealed that elevated Tim-4 expression was strongly linked to distant metastasis, TNM stage and reduced overall survival duration in CRC patients. (Source: Cancer Letters)
Source: Cancer Letters - August 14, 2018 Category: Cancer & Oncology Authors: Xiao Tan, Zhongqiang Zhang, Hongliang Yao, Liangfang Shen Tags: Original Articles Source Type: research

Exosomal Transfer of miR-151a Enhances Chemosensitivity to Temozolomide in Drug-resistant Glioblastoma
Chemoresistance blunts the effect of Temozolomide (TMZ) in the treatment of glioblastoma multiforme (GBM). Whether exosomal transfer of miRNAs derived from TMZ-resistant GBM cells could confer TMZ resistance remains to be determined. qPCR was used to determine miR-151a expression in two TMZ-resistant GBM cell lines. The direct targets of miR-151a were identi fied by microarray assays, bioinformatics and further RNA chromatin immunoprecipitation (RNA-ChIP) assay. We characterized exosomes from TMZ-resistant cell lines, serum and cerebrospinal fluid (CSF) and determined the effect of exosomes from TMZ-resistant cells on rec...
Source: Cancer Letters - August 10, 2018 Category: Cancer & Oncology Authors: Ailiang Zeng, Zhiyun Wei, Wei Yan, Jianxing Yin, Xiaoxu Huang, Xu Zhou, Rui Li, Feng Shen, Weining Wu, Xiefeng Wang, Yongping You Tags: Original Articles Source Type: research

Fatty Acid Oxidation: An Emerging Facet of Metabolic Transformation in Cancer
Cancer cells undergo metabolic reprogramming such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid cycle enzymes, and upregulation of de novo lipid synthesis and glutaminolysis. These alterations are pivotal to the development and maintenance of the malignant phenotype of cancer cells in unfavorable tumor microenvironment or metastatic sites. Although mitochondrial fatty acid β-oxidation (FAO) is a primary bioenergetic source, it has not been generally recognized as part of the metabolic landscape of cancer. (Source: Cancer Letters)
Source: Cancer Letters - August 10, 2018 Category: Cancer & Oncology Authors: Yibao Ma, Sarah M. Temkin, Adam M. Hawkridge, Chunqing Guo, Wei Wang, Xiang-Yang Wang, Xianjun Fang Tags: Mini-review Source Type: research

Exosomes derived from hypoxic epithelial ovarian cancer cells deliver microRNAs to macrophages and elicit a tumor-promoted phenotype
In this study, we revealed that exosomes derived from EOC cells remodel macrophages to a tumor-promoted phenotype, namely TAMs. In addition, hypoxic microenvironments have been postulated to facilitate this process in the TME, and hypoxia-inducible factors (HIFs) play an important role in this process. (Source: Cancer Letters)
Source: Cancer Letters - August 8, 2018 Category: Cancer & Oncology Authors: Xin Chen, Jieru Zhou, Xiaoduan Li, Xinjing Wang, Yingying Lin, Xipeng Wang Tags: Original Articles Source Type: research

cAMP/PKA-induced filamin A (FLNA) phosphorylation inhibits SST2 signal transduction in GH-secreting pituitary tumor cells
An efficient intracellular response to somatostatin analogs (SSA) in pituitary tumors requires filamin A (FLNA). Since cAMP pathway plays an important role in GH-secreting pituitary tumors pathogenesis and FLNA is phosphorylated by PKA on S2152, aim of this study was to investigate in tumoral somatotrophs the impact of cAMP pathway activation and SSA stimulation on FLNA phosphorylation and the consequences on SST2 function.We found a PKA-mediated increase (2-fold) and SST2 agonist-induced decrease (-50%) of FLNA phosphorylation in GH3, GH4C1 and primary somatotroph tumor cells. (Source: Cancer Letters)
Source: Cancer Letters - August 8, 2018 Category: Cancer & Oncology Authors: E. Peverelli, E. Giardino, F. Mangili, D. Treppiedi, R. Catalano, E. Ferrante, E. Sala, M. Locatelli, A.G. Lania, M. Arosio, A. Spada, G. Mantovani Tags: Original Articles Source Type: research

Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt-dependent tumors through a direct effect on secreted Wnts
We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells. (Source: Cancer Letters)
Source: Cancer Letters - August 8, 2018 Category: Cancer & Oncology Authors: Alexey Koval, Constant A. Pieme, Emerson Ferreira Queiroz, Simone Ragusa, Kamal Ahmed, Artem Blagodatski, Jean-Luc Wolfender, Tatiana V. Petrova, Vladimir L. Katanaev Tags: Original Articles Source Type: research

β-catenin contributes to cordycepin-induced MGMT inhibition and reduction of temozolomide resistance in glioma cells by increasing intracellular reactive oxygen species
Glioblastoma multiforme (GBM) is one of the most aggressive human tumors, and it has a poor prognosis. Temozolomide (TMZ) is the primary alkylating agent used to treat GBM. Nevertheless, a number of GBM patients are resistant to TMZ. Therefore, there is an urgent need for more effective therapeutic options. Cordycepin (COR) is a natural chemical with anti-tumor effects, although its mechanism of action is poorly understood. Several lines of evidence suggest that O6-methylguanine DNA methyltransferase (MGMT) repairs damaged DNA and contributes to drug resistance to TMZ in gliomas. (Source: Cancer Letters)
Source: Cancer Letters - August 3, 2018 Category: Cancer & Oncology Authors: Yiming Bi, Han Li, Dazhuang Yi, Yang Bai, Sheng Zhong, Qiaochu Liu, Yong Chen, Gang Zhao Tags: Original Articles Source Type: research

S100B Suppression Alters Polarization of Infiltrating Myeloid-Derived Cells in Gliomas and Inhibits Tumor Growth
S100B, a member of the multigene family of Ca2+-binding proteins, is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. Recently, we demonstrated that low concentrations of S100B attenuated microglia activation through the induction of STAT3. Furthermore, S100B downregulation in a murine glioma model inhibited macrophage trafficking and tumor growth. Based on these observations, we hypothesized that S100B inhibitors may have antiglioma properties through modulation of tumor microenvironment. (Source: Cancer Letters)
Source: Cancer Letters - August 2, 2018 Category: Cancer & Oncology Authors: Hang Gao, Ian Y. Zhang, Leying Zhang, Yanyan Song, Shunan Liu, Hui Ren, Huili Liu, Hui Zhou, Yanping Su, Yihang Yang, Behnam Badie Tags: Original Articles Source Type: research

Novel CIL-102 Derivatives as Potential Therapeutic Agents for Docetaxel-Resistant Prostate Cancer
In this study, we modified the structure of CIL-102 and investigated the efficacy of the derivatives against CRPC and docetaxel-resistant PCa. (Source: Cancer Letters)
Source: Cancer Letters - August 2, 2018 Category: Cancer & Oncology Authors: Dannah R. Miller, Cherng-Chyi Tzeng, Trey Farmer, Evan T. Keller, Steve Caplan, Yu-Shuin Chen, Yeh-Long Chen, Ming-Fong Lin Tags: Original Articles Source Type: research

Hypertonicity-imposed BCL-XL addiction primes colorectal cancer cells for death
Induction of mitochondria-controlled (intrinsic) apoptosis is a mainstay of current anti-neoplastic chemotherapies. Activation of this death pathway is counteracted by BCL-2-like proteins, which functionally set the threshold for apoptosis and determine whether malignant cells are sensitive or resistant to anti-cancer treatments. Hence, unlocking the intrinsic apoptotic cascade and promoting the cell's commitment to undergo apoptosis concordantly promotes efficacy of anti-cancer treatments. Here, we show that hyperosmotic stress enforces addiction of colorectal cancer cells to BCL-XL, thereby exhausting the protective capa...
Source: Cancer Letters - August 1, 2018 Category: Cancer & Oncology Authors: Sina Heimer, Gertrud Knoll, Charlotte Steixner, Diana Nicoleta Calance, Dieu Thuy Trinh, Martin Ehrenschwender Tags: Original Articles Source Type: research

TRIM65 supports bladder urothelial carcinoma cell aggressiveness by promoting ANXA2 ubiquitination and degradation
In this study, TRIM65 was first screened as an important oncogenic factor of UCB from the Cancer Genome Atlas (TCGA) database and was validated by a large cohort of clinical UCB tissues. (Source: Cancer Letters)
Source: Cancer Letters - August 1, 2018 Category: Cancer & Oncology Authors: Wen-Su Wei, Xin Chen, Li-Yi Guo, Xiang-Dong Li, Ming-Hui Deng, Gang- Jun Yuan, Le-Ye He, Yong-Hong Li, Zhi-Lin Zhang, Li-Juan Jiang, Ri-Xin Chen, Xiao-Dan Ma, Shi Wei, Ning-Fang Ma, Zhuo-Wei Liu, Jun-Hang Luo, Fang-Jian Zhou, Dan Xie Tags: Original Articles Source Type: research

Exosomes in cancer: Small transporters with big functions
Exosomes are nanosized membrane-bound vesicles containing abundant proteins, DNA, mRNA, and non-coding RNAs. Exosomes are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Increasing studies have shown that exosomes play an important role in tumour initiation, growth, progression, metastasis, drug resistance and immune escape. In this article, we review recent advances in the biology of exosomes. We elaborate the specific mechanism by which exosomes affect the communication between tumours and the microenvironment. (Source: Cancer Letters)
Source: Cancer Letters - July 30, 2018 Category: Cancer & Oncology Authors: Xi Li, Yanan Wang, Qi Wang, Yinping Liu, Wei Bao, Sufang Wu Tags: Mini-review Source Type: research

Co-inhibition of BET and proteasome enhances ER stress and Bim-dependent apoptosis with augmented cancer therapeutic efficacy
Agents that inhibit bromodomain and extra-terminal domain (BET) protein have been actively tested in the clinic as potential anticancer drugs. Proteasome inhibitors such as carfilzomib (CFZ) are FDA-approved for the treatment of patients with advanced multiple myeloma and have been tested against other cancers. The current study focuses on the combination of a BET inhibitor (e.g., JQ1) and a proteasome inhibitor (e.g., CFZ) as a novel cancer therapeutic strategy and the underlying mechanisms. The tested combination (JQ1 with CFZ) synergistically decreased cell survival and enhanced apoptosis in vitro and inhibited tumor gr...
Source: Cancer Letters - July 27, 2018 Category: Cancer & Oncology Authors: Guoqing Qian, Weilong Yao, Shuo Zhang, Richa Bajpai, Williams D. Hall, Mala Shanmugam, Sagar Lonial, Shi-Yong Sun Tags: Original Articles Source Type: research

Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - July 26, 2018 Category: Cancer & Oncology Source Type: research

miR-1273g silences MAGEA3/6 to inhibit human colorectal cancer cell growth via activation of AMPK signaling
AMP-activated protein kinase (AMPK) is a metabolic regulator that acts to limit the growth of cancer cells. AMPK is downregulated by melanoma antigens A3/6 (MAGEA3/6), which are cancer-specific proteins that enhance the activity of specific E3 ubiquitin ligases to ubiquitinate and degrade AMP-activated protein kinase α1 (AMPKα1). Here, using a bioinformatic approach, we identified a microRNA, miR-1273 g-3p, that is predicted to target the 3’ untranslated region (UTR) of MAGEA3/6. Analyzing miR-1273 g-3p expression in human colon cancer tissues, we found a reduction in miR-1273 g-3p expression correl...
Source: Cancer Letters - July 26, 2018 Category: Cancer & Oncology Authors: Fang Wu, Fang Liu, Lemei Dong, Han Yang, Xixi He, Lili Li, Lihao Zhao, Sisi Jin, Gang Li Tags: Original Articles Source Type: research

USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma
Dysregulation of deubiquitination pathway is associated with poor prognosis in cancers such as hepatocellular carcinoma (HCC). The mammalian target of rapamycin, mTOR, has become an attractive cancer therapeutic target in HCC. However, whether and how aberrant expression of deubiquitination pathway regulates mTOR pathway has remained elusive. Here we report that ubiquitin-specific protease 10 (USP10) functions as a tumor suppressor which inhibits mTOR pathway by stabilizing PTEN and AMPK α in HCC cells. (Source: Cancer Letters)
Source: Cancer Letters - July 26, 2018 Category: Cancer & Oncology Authors: Chang Lu, Zhen Ning, Aman Wang, Di Chen, Xiaolong Liu, Tian Xia, Dinesh Singh Tekcham, Wen Wang, Tongming Li, Xiumei Liu, Jing Liu, Huan Qi, Haifeng Luo, Jian Du, Chi Ma, Qiu Yan, Jiwei Liu, Guowang Xu, Hai-long Piao, Guang Tan Tags: Original Articles Source Type: research

Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to Sunitinib
In this study we systematically screened a library of 306 known anti-cancer drugs for their ability to induce autophagy using a cell-based assay. 114 of the drugs were classified as autophagy inducers; for 16 drugs, the cytotoxicity was potentiated by siRNA-mediated knock-down of Atg7 and Vps34. These drugs were further evaluated in breast cancer cell lines for autophagy induction, and two tyrosine kinase inhibitors, Sunitinib and Erlotinib, were selected for further studies. (Source: Cancer Letters)
Source: Cancer Letters - July 25, 2018 Category: Cancer & Oncology Authors: Matheus Dyczynski, Yasmin Yu, Magdalena Otrocka, Santiago Parpal, Tiago Braga, Aine Brigette Henley, Henric Zazzi, Mikael Lerner, Krister Wennerberg, Jenny Viklund, Jessica Martinsson, Dan Grand ér, Angelo De Milito, Katja Pokrovskaja Tamm Tags: Original Articles Source Type: research

Junctional adhesion molecules mediate transendothelial migration of dendritic cell vaccine in cancer immunotherapy
In vitro generated dendritic cells (DCs) have been studied in cancer immunotherapy for decades. However, the detailed molecular mechanism underlying transendothelial migration (TEM) of DC vaccine across the endothelial barrier to regional lymph nodes (LNs) remains largely unknown. Here, we found that junctional adhesion molecule (JAM)-Like (JAML) is involved in the TEM of mouse bone marrow-derived DCs (BMDCs). Treatment with an anti-JAML antibody or JAML knock-down significantly reduced the TEM activity of BMDCs, leading to impairment of DC-based cancer immunotherapy. (Source: Cancer Letters)
Source: Cancer Letters - July 25, 2018 Category: Cancer & Oncology Authors: Seung-Eon Roh, Yideul Jeong, Myeong-Ho Kang, Yong-Soo Bae Tags: Original Articles Source Type: research

Viewing the Eph Receptors with a focus on Breast Cancer Heterogeneity
Aberrant expression of different family members of the Eph/ephrin system, which comprises the Eph receptors (Ephs) and their ligands (ephrins), has been implicated in various malignancies including breast cancer. The latter presents as a heterogeneous disease with diverse molecular, morphologic and clinical behavior signatures. This review reflects the existing Eph/ephrin literature while focusing on breast cancer heterogeneity. Hormone positive, HER2 positive and triple negative breast cancer (TNBC) cell lines, xenografts/mutant animal models and patient samples are examined separately as, in humans, they represent entiti...
Source: Cancer Letters - July 25, 2018 Category: Cancer & Oncology Authors: Ilias Nikas, Han Suk Ryu, Stamatios Theocharis Tags: Mini-review Source Type: research

Recent findings regarding let-7 in immunity
Let-7 was one of the first microRNAs discovered in Caenorhabditis elegans. It exerts various biological functions, and shows strong evolutionary conservation from nematodes to humans. Recent research findings identify the let-7 cluster as a crucial player in the regulation of B-cell antibody production and macrophage responses. Since increasing evidence supports the let-7 cluster's role in immune system regulation, here we review the latest knowledge regarding the activities of let-7 in both innate and adaptive immune cells —including macrophages, B cells, and subsets of T cells—and the targets regulated by mem...
Source: Cancer Letters - July 24, 2018 Category: Cancer & Oncology Authors: Shuai Jiang Tags: Mini-review Source Type: research

Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells
GFRA1 and RET are overexpressed in estrogen receptor (ER)-positive breast cancers. Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes. Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported. We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells. (Source: Cancer Letters)
Source: Cancer Letters - July 21, 2018 Category: Cancer & Oncology Authors: Tan-chi Fan, Hui Ling Yeo, Huan-Ming Hsu, Jyh-Cherng Yu, Ming-Yi Ho, Wen-Der Lin, Nai-Chuan Chang, John Yu, Alice L. Yu Tags: Original Articles Source Type: research

Inhibiting Notch1 enhances immunotherapy efficacy in melanoma by preventing Notch1 dependent immune suppressive properties
We have previously shown that Notch1 plays a critical role in modulating melanoma tumor cell growth and survival. Here we show that Notch1 also contributes to an immune-suppressive tumor microenvironment (TME). Notch1 inhibition reduces immune suppressive cells (i.e. MDSCs and Tregs) while allowing the recruitment of functional CD8(+) T cells, leading to a decrease in the Tregs/CD8(+) ratio, a key parameter in assessing positive responses to immune-checkpoint inhibitors. Inhibition of Notch1 improves the antitumor activity of nivolumab and ipilimumab, particularly when given in combination. (Source: Cancer Letters)
Source: Cancer Letters - July 20, 2018 Category: Cancer & Oncology Authors: Hong Qiu, Patrick M. Zmina, Alex Y. Huang, David Askew, Barbara Bedogni Tags: Original Articles Source Type: research

mTORC2 contributes to the metabolic reprogramming in EGFR tyrosine-kinase inhibitor resistant cells in non-small cell lung cancer
Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations are often successfully treated with EGFR tyrosine kinase inhibitor (TKI) such as erlotinib; however, treatment resistance inevitably occurs. Given tumor metabolism of glucose and therapeutic response are intimately linked, we explored the metabolic differences between isogenic erlotinib-sensitive and -resistant NSCLC cell lines. We discovered that the growth of erlotinib-resistant cells is more sensitive to glucose deprivation. (Source: Cancer Letters)
Source: Cancer Letters - July 20, 2018 Category: Cancer & Oncology Authors: Chun-Te Chiang, Alexandra N. Demetriou, Nolan Ung, Niharika Choudhury, Kimya Ghaffarian, Daniel L. Ruderman, Shannon M. Mumenthaler Tags: Original Articles Source Type: research

Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein
Cholangiocarcinoma (CCA) is a destructive malignancy with limited responsiveness to conventional chemotherapy. Although angiotensin receptor blockers (ARBs) have gained attention for their potential anticancer activity, little is known about their effects on CCA. The transcriptional co-activator, Yes-associated protein (YAP) is a critical oncogene in several cancers, including CCA. Following recent evidence showing that YAP is regulated by angiotensin II (AT-II), we investigated the effects of an ARB, losartan, on two human CCA cell lines (KKU-M213 and HuCCT-1) with regards to YAP oncogenic regulation. (Source: Cancer Letters)
Source: Cancer Letters - July 19, 2018 Category: Cancer & Oncology Authors: Soichiro Saikawa, Kosuke Kaji, Norihisa Nishimura, Kenichiro Seki, Shinya Sato, Keisuke Nakanishi, Koh Kitagawa, Hideto Kawaratani, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Akira Mitoro, Hitoshi Yoshiji Tags: Original Articles Source Type: research

Genome-wide identification of transcription factors that are critical to non-small cell lung cancer
To systematically unveil transcription factors (TFs) that are critical to lung carcinogenesis, here we conducted a genome-wide lethality screening in non-small cell lung cancer (NSCLC) cells and reported that among the 1530  TFs tested, 21 genes were required for NSCLC cell proliferation and were negatively or positively associated with overall survival (OS) of patients with NSCLC. These included 11 potential tumor suppressing genes (AFF3, AhR, AR, CBFA2T3, CHD4, KANK2, NR3C2, PTEN, PRDM16, RB1, and STK11) and 10 pot ential oncogenic TFs (BARX1, DLX6, ELF3, EN1, ETV1, FOXE1, HOXB7, IRX4, IRX5, and SALL1). (Source: Cancer Letters)
Source: Cancer Letters - July 18, 2018 Category: Cancer & Oncology Authors: Da-Lin Zhang, Li-Wei Qu, Liang Ma, Yong-Chun Zhou, Gui-Zhen Wang, Xin-Chun Zhao, Chen Zhang, Yan-Fei Zhang, Min Wang, Mei-Ying Zhang, Hong Yu, Bei-Bei Sun, San-Hui Gao, Xin Cheng, Ming-Zhou Guo, Yun-Chao Huang, Guang-Biao Zhou Tags: Original Articles Source Type: research

The positive inotropic agent DPI-201106 selectively reverses ABCB1-mediated multidrug resistance in cancer cell lines
The overexpression of ABCB1 in cancer cells is a major factor contributing to the development of multidrug resistance (MDR) and treatment failure in cancer patients. Therefore, re-sensitization of MDR cancer cells to anticancer drugs remains an important aspect in chemotherapy. The progress in developing clinically applicable synthetic inhibitors of ABCB1 has been slow, mostly due to complications associated with intrinsic toxicities and unforeseen drug-drug interactions. Here, we explored the drug-repositioning approach for cancer therapy by targeting ABCB1-mediated MDR in human cancer cells. (Source: Cancer Letters)
Source: Cancer Letters - July 18, 2018 Category: Cancer & Oncology Authors: Sung-Han Hsiao, Megumi Murakami, Ni Yeh, Yan-Qing Li, Tai-Ho Hung, Yu-Shan Wu, Suresh V. Ambudkar, Chung-Pu Wu Tags: Original Articles Source Type: research

Patient Derived Xenografts as Models for Head and Neck Cancer
Translational cancer research has benefitted significantly from the generation of preclinical models that recapitulate the native tumour environment. While conventional cell models have contributed substantially to the current understanding of cancer biology and therapeutic development, a missing link between cell culture and their clinical applications is evident. Patient derived xenograft (PDX) models represent this missing link as they enable the examination of patient tumour tissue in a native environment without significantly affecting the cellular complexity, genomics, and stromal architecture of the neoplasms. (Source: Cancer Letters)
Source: Cancer Letters - July 18, 2018 Category: Cancer & Oncology Authors: Nitschinsk Km, Idris A, McMillan Na Tags: Mini-review Source Type: research

LncRNA-p23154 promotes the invasion-metastasis potential of oral squamous cell carcinoma by regulating Glut1-mediated glycolysis
In this study, we identified a novel lncRNA lnc-p23154 which is associated with OSCC patient metastasis and the promotion of OSCC cell migration and invasion in vitro and in vivo. (Source: Cancer Letters)
Source: Cancer Letters - July 17, 2018 Category: Cancer & Oncology Authors: Yun Wang, Xiaojie Zhang, Zhi Wang, Qinchao Hu, Jie Wu, Yuanyuan Li, Xianyue Ren, Tong Wu, Xiaoan Tao, Xiaobing Chen, Xiaoxu Li, Juan Xia, Bin Cheng Tags: Original Articles Source Type: research

Relevance of the natural HDAC inhibitor sulforaphane as a chemopreventive agent in urologic tumors
Due to an increased understanding of molecular biology and the genomics of cancer, new and potent agents have been approved by the Food and Drug Administration (FDA) to fight this disease. However, all of these drugs cause severe side effects and resistance inevitably develops, re-activating tumor growth and dissemination. For this reason, patients turn to natural compounds as alternative or complementary treatment options, since it has been found that natural plant products may block, inhibit, or reverse cancer development. (Source: Cancer Letters)
Source: Cancer Letters - July 17, 2018 Category: Cancer & Oncology Authors: Eva Juengel, Holger H.H. Erb, Axel Haferkamp, Jochen Rutz, Felix K.-H. Chun, Roman A. Blaheta Source Type: research

Targeting Ubiquitin-proteasome pathway by natural, in particular polyphenols, anticancer agents: lessons learned from clinical trials
The ubiquitin-proteasome pathway (UPP) is the main non-lysosomal proteolytic system responsible for degradation of most intracellular proteins, specifically damaged and regulatory proteins. The UPP is implicated in all aspects of the cellular metabolic networks including physiological or pathological conditions. Alterations in the components of the UPP can lead to stabilization of oncoproteins or augmented degradation of tumour suppressor favouring cancer appearance and progression. Polyphenols are natural compounds that can modulate proteasome activity or the expression of proteasome subunits. (Source: Cancer Letters)
Source: Cancer Letters - July 17, 2018 Category: Cancer & Oncology Authors: Seyed Fazel Nabavi, Atanas G. Atanasov, Haroon Khan, Davide Barreca, Domenico Trombetta, Lara Testai, Antoni Sureda, Silvia Tejada, Rosa Anna Vacca, Valeria Pittala, Diana Gulei, Ioana Berindan-Neagoe, Samira Shirooie, Seyed Mohammad Nabavi Source Type: research

Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment
Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Nucleos(t)ide analogue (NA) therapy effectively reduces the incidence of HCC, but it does not completely prevent the disease. Here, we show that dysregulation of microRNAs (miRNAs) is involved in post-NA HCC development. We divided chronic hepatitis B (CHB) patients who received NA therapy into two groups: 1) those who did not develop HCC during the follow-up period after NA therapy (no-HCC group) and 2) those who did (HCC group). (Source: Cancer Letters)
Source: Cancer Letters - July 16, 2018 Category: Cancer & Oncology Authors: Hideki Wakasugi, Hideaki Takahashi, Takeshi Niinuma, Hiroshi Kitajima, Ritsuko Oikawa, Naoki Matsumoto, Yuko Takeba, Takehito Otsubo, Masayuki Takagi, Yasushi Ariizumi, Michihiro Suzuki, Chiaki Okuse, Shogo Iwabuchi, Masayuki Nakano, Noriyuki Akutsu, Jong Tags: Original Articles Source Type: research

2 ’-Hydroxycinnamaldehyde inhibits cancer cell proliferation and tumor growth by targeting the pyruvate kinase M2
In this study, we identified pyruvate kinase M2 (PKM2) as a direct target of HCA by use of biochemical methods including affinity chromatography, drug affinity responsive target stability, and cellular thermal shift assay. PKM2 is up-regulated in multiple cancer types and is considered as a potential target for cancer therapy. HCA binds directly to PKM2 and selectively decreases the phosphorylation of PKM2 at Tyr105, indicating a potential anti-proliferative effect on prostate cancer cells. (Source: Cancer Letters)
Source: Cancer Letters - July 15, 2018 Category: Cancer & Oncology Authors: Yae Jin Yoon, Young-Hwan Kim, Yena Jin, Seung-Wook Chi, Jeong Hee Moon, Dong Cho Han, Byoung-Mog Kwon Tags: Original Articles Source Type: research

Retraction notice to “Sun exposure related methylation in malignant and non-malignant skin lesions” [Cancer Letters 245/1-2 (2007) 112-120]
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). (Source: Cancer Letters)
Source: Cancer Letters - July 12, 2018 Category: Cancer & Oncology Authors: Ubaradka G. Sathyanarayana, Angela Yen Moore, Lin Li, Asha Padar, Kuntal Majmudar, Victor Stastny, Prakash Makarla, Makoto Suzuki, John D. Minna, Ziding Feng, Adi F. Gazdar Source Type: research

Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - July 12, 2018 Category: Cancer & Oncology Source Type: research

DCZ3112, a novel Hsp90 inhibitor, exerts potent antitumor activity against HER2-positive breast cancer through disruption of Hsp90-Cdc37 interaction
In this study, we discovered a new Hsp90 inhibitor, DCZ3112, with a novel mechanism of action. DCZ3112 directly bound to the N-terminal domain of Hsp90 and inhibited Hsp90-Cdc37 interaction without inhibiting ATPase activity. (Source: Cancer Letters)
Source: Cancer Letters - July 12, 2018 Category: Cancer & Oncology Authors: Xiangling Chen, Peng Liu, Quanren Wang, Yun Li, Li Fu, Haoyu Fu, Jianming Zhu, Zhaoqiang Chen, Weiliang Zhu, Chengying Xie, Liguang Lou Tags: Original Articles Source Type: research

Telomerase reverse transcriptase regulates DNMT3B expression/aberrant DNA methylation phenotype and AKT activation in hepatocellular carcinoma
Telomerase reverse transcriptase (TERT)1 acts as a master regulator of cancer hallmarks, but underlying mechanisms remain incompletely understood. We show that TERT is required for the aberrant DNA methyltransferase 3  B (DNMT3B)2 expression and cancer-specific methylation in hepatocellular carcinoma (HCC)3, through which AKT is activated. TERT depletion inhibited, while its over-expression promoted DNMT3B expression in HCC cells, respectively. Mechanistically, TERT cooperates with the transcription factor Sp1 to stimulate DNMT3B transcription. (Source: Cancer Letters)
Source: Cancer Letters - July 12, 2018 Category: Cancer & Oncology Authors: Jingya Yu, Xiaotian Yuan, Louise Sj öholm, Tiantian Liu, Feng Kong, Tomas J. Ekström, Magnus Björkholm, Dawei Xu Tags: Original Articles Source Type: research

Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation
Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. (Source: Cancer Letters)
Source: Cancer Letters - July 9, 2018 Category: Cancer & Oncology Authors: Suleman S. Hussain, Shih-Bo Huang, Roble G. Bedolla, Paul Rivas, Joseph W. Basler, Gregory P. Swanson, Tim Hui-Ming Huang, Ganesh Narayanasamy, Nikos Papanikolaou, Hiroshi Miyamoto, I-Tien Yeh, Robert L. Reddick, Brad H. Pollock, Rita Ghosh, Addanki P. Ku Tags: Original Articles Source Type: research

Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3K α-selective inhibitor CYH33 in breast cancer
PI3Ks are frequently hyper-activated in breast cancer and targeting PI3K α has exhibited promising but variable response in preclinical and clinical settings. CYH33 is a novel PI3Kα-selective inhibitor in phase I clinical trial. We investigated the efficacy of CYH33 against breast cancer and explored potential predictive biomarkers. CYH33 potently restrained tumor grow th in mice bearing human breast cancer cell xenografts and in R26-Pik3caH1047R;MMTV-Cre transgenic mice. CYH33 significantly inhibited proliferation of a panel of human breast cancer cells, while diversity in sensitivity has been observed. (Source: Cancer Letters)
Source: Cancer Letters - July 9, 2018 Category: Cancer & Oncology Authors: Xue-ling Liu, Yi-chao Xu, Yu-xiang Wang, Yi Chen, Bo-bo Wang, Yi Wang, Lan-ding Hu, Qing-yang Ma, Yu-chao Zhang, Yi-ming Sun, Ying-lei Gao, Chun-hao Yang, Jian Ding, Ling-hua Meng Tags: Original Articles Source Type: research

Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells
Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor. The current standard therapy, which includes radiation and chemotherapy, is frequently ineffective partially because of drug resistance and poor penetration of the blood-brain barrier. Reducing resistance and increasing sensitivity to chemotherapy may improve outcomes. Glioma stem cells (GSCs) are a source of relapse and chemoresistance in GBM; sensitization of GSCs to temozoliomide (TMZ), the primary chemotherapeutic agent used to treat GBM, is therefore integral for therapeutic efficacy. (Source: Cancer Letters)
Source: Cancer Letters - July 6, 2018 Category: Cancer & Oncology Authors: Hyangsoon Noh, Qingnan Zhao, Jun Yan, Ling-Yuan Kong, Konrad Gabrusiewicz, Sungguan Hong, Xueqing Xia, Amy B. Heimberger, Shulin Li Tags: Original Articles Source Type: research

SIS3, a specific inhibitor of Smad3 reverses ABCB1- and ABCG2-mediated multidrug resistance in cancer cell lines
One of the major challenges in cancer chemotherapy is the development of multidrug resistance phenomenon attributed to the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2 in cancer cells. Therefore, re-sensitizing MDR cancer cells to chemotherapy by directly inhibiting the activity of ABC transporters has clinical relevance. Unfortunately, previous attempts of developing clinically applicable synthetic inhibitors have failed, mostly due to problems associated with toxicity and unforeseen drug-drug interactions. (Source: Cancer Letters)
Source: Cancer Letters - July 6, 2018 Category: Cancer & Oncology Authors: Chung-Pu Wu, Megumi Murakami, Sung-Han Hsiao, Te-Chun Liu, Ni Yeh, Yan-Qing Li, Tai-Ho Hung, Yu-Shan Wu, Suresh. V. Ambudkar Tags: Original Articles Source Type: research

Cell surface vimentin –targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells
Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor. The current standard therapy, which includes radiation and chemotherapy, is frequently ineffective partially because of drug resistance and poor penetration of the blood-brain barrier. Reducing resistance and increasing sensitivity to chemotherapy may improve outcomes. Glioma stem cells (GSCs) are a source of relapse and chemoresistance in GBM; sensitization of GSCs to temozoliomide (TMZ), the primary chemotherapeutic agent used to treat GBM, is therefore integral for therapeutic efficacy. (Source: Cancer Letters)
Source: Cancer Letters - July 6, 2018 Category: Cancer & Oncology Authors: Hyangsoon Noh, Qingnan Zhao, Jun Yan, Ling-Yuan Kong, Konrad Gabrusiewicz, Sungguan Hong, Xueqing Xia, Amy B. Heimberger, Shulin Li Tags: Original Articles Source Type: research

Delivery of MGMT mRNA to glioma cells by reactive astrocyte-derived exosomes confers a temozolomide resistance phenotype
In this study, we show that glioma cells stimulate normal human astrocyte (NHA) into reactive astrocyte (RAS) in a non-contact manner. Additionally, the amount of O6-alkylguanine DNA alkyltransferase (MGMT) mRNA in exosomes (EXOs) released by RAS was significantly increased compared with that in non-reactive NHA. Importantly, MGMT-negative glioma cells can take up RAS-EXOs and acquire a temozolomide (TMZ)-resistant phenotype via the translation of exogenous exosomal MGMT mRNA both in vitro and in vivo. (Source: Cancer Letters)
Source: Cancer Letters - July 6, 2018 Category: Cancer & Oncology Authors: Tianfu Yu, XieFeng Wang, Tongle Zhi, Junxia Zhang, Yingyi Wang, Er Nie, Fengqi Zhou, Yongping You, Ning Liu Tags: Original Articles Source Type: research

Prolactin signaling drives tumorigenesis in human high grade serous ovarian cancer cells and in a spontaneous fallopian tube derived model
The pathways responsible for tumorigenesis of high grade serous ovarian cancer (HGSOC) from the fallopian tube epithelium (FTE) are still poorly understood. A human prolactin (PRL) like gene, Prl2c2 was amplified>100 fold in a spontaneous model of FTE-derived ovarian cancer (MOEhigh - murine oviductal epithelium high passage). Prl2c2 stable knockdown in MOEhigh cells demonstrated a significant reduction in cell proliferation, 2-dimensional foci, anchorage independent growth, and completely blocked tumor formation. (Source: Cancer Letters)
Source: Cancer Letters - July 5, 2018 Category: Cancer & Oncology Authors: Subbulakshmi Karthikeyan, Angela Russo, Matthew Dean, Daniel D. Lantvit, Michael Endsley, Joanna E. Burdette Tags: Original Articles Source Type: research

The dual role of mast cells in tumor fate
The exact role of mast cells in tumor growth is not clear and multifaceted. In some cases, mast cells stimulate while in others inhibit this process. This dual role may be explained to some extent by the huge number of bioactive molecules stored in mast cell granules, as well as differences between tumor microenvironment, tumor type, and tumor phase of development. (Source: Cancer Letters)
Source: Cancer Letters - July 5, 2018 Category: Cancer & Oncology Authors: Domenico Ribatti, Roberto Tamma Tags: Mini-review Source Type: research

Advances in Oncolytic Adenovirus Therapy for Pancreatic Cancer
Survival rates for pancreatic cancer patients have remained unchanged for the last four decades. The most aggressive, and most common, type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which has the lowest 5-year survival rate of all cancers globally. The poor prognosis is typically due to late presentation of often non-specific symptoms and rapid development of resistance to all current therapeutics, including the standard-of-care cytotoxic drug gemcitabine. While early surgical intervention can significantly prolong patient survival, there are few treatment options for late-stage non-resectable metast...
Source: Cancer Letters - July 5, 2018 Category: Cancer & Oncology Authors: Callum Nattress, Gunnel Halld én Tags: Mini-review Source Type: research