Sonic hedgehog signaling pathway mediates development of hepatocellular carcinoma
AbstractAlthough abnormal activation of the sonic hedgehog (Shh) signaling pathway has been demonstrated in human hepatocellular carcinoma (HCC) patients and in most HCC cell lines, the mechanism by which the Shh pathway promotes the development of HCC remains uncertain. Using a liver cancer model induced by diethylnitrosamine (DEN) which mimics the process from liver injury, abnormal hepatocyte proliferation, and hepatocirrhosis to hepatocyte canceration, we investigated the abnormal activation of the Shh pathway by examining the expression of Shh, patched-1 (Ptch), smoothened (SMO), and glioma-associated oncogene-1 (Gli1...
Source: Tumor Biology - October 14, 2016 Category: Cancer & Oncology Source Type: research
RAD51 regulates CHK1 stability via autophagy to promote cell growth in esophageal squamous carcinoma cells
AbstractThe serine/threonine protein kinase CHK1 has been reported to bind to the recombinase RAD51 and facilitates its assembly in DNA damage sites via phosphorylation. However, the role of RAD51 in regulating the expression of CHK1 has never been explored. Here, we show that RAD51 is highly upregulated in esophageal squamous tumor tissues and its DMC1 domain significantly promotes cell growth of esophageal cancer (EC) cells through CHK1. To gain the mechanistic insights, firstly, in the presence of 3-methyladenine (3MA), an autophagy inhibitor, we found that the reduction of CHK1 and the inhibition of cell growth in RAD5...
Source: Tumor Biology - October 13, 2016 Category: Cancer & Oncology Source Type: research
LncRNA GAS5 inhibits proliferation and progression of prostate cancer by targeting miR-103 through AKT/mTOR signaling pathway
This study aims to clarify the underlying mechanisms of lncRNA GAS5 in prostate cancer (PCa). In total, 118 pairs of PCa tissues and matched adjacent non-tumor tissues were collected. Additionally, lncRNA GAS5 exposure levels were determined using RT-PCR and in situ hybridization. In addition, dual-luciferase report assay was performed to verify the target effect of lncRNA GAS5 on miR-103. The exposure levels of the proteins related to the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis, including AKT, mTOR, and S6K1, were measured by western blot PC3 cells infected with lncRNA GAS5 mimic; lncRNA GAS5 siRN...
Source: Tumor Biology - October 13, 2016 Category: Cancer & Oncology Source Type: research
MMP inhibitor Ilomastat induced amoeboid-like motility via activation of the Rho signaling pathway in glioblastoma cells
AbstractMatrix metalloproteinases (MMPs) play the important role in the process of glioblastoma cell invasion through 3D matrices. However, the effects of MMP inhibitors used in the treatment of malignant gliomas are unsatisfactory. The aim of this study was to explore the reason and mechanism by which cells move through the dense extracellular matrix without proteolysis. The results showed that MMP inhibitor (MMPI), Ilomastat, induced glioma cells to have an amoeboid-like morphology with invasive ability. Moreover, the RhoA/Rho kinase (ROCK)/myosin light chain (MLC) signal is involved in the MMPI-induced movement mode swi...
Source: Tumor Biology - October 13, 2016 Category: Cancer & Oncology Source Type: research
Differential miRNA expression in pleural effusions derived from extracellular vesicles of patients with lung cancer, pulmonary tuberculosis, or pneumonia
AbstractMicroRNAs (miRNAs) have been found to play important regulatory roles in various physiological and pathological processes. MiRNAs also exhibit high stability and are present at high concentrations in human bodily fluids. Consequently, miRNAs may represent attractive and novel diagnostic biomarkers for certain clinical conditions. Recently, the capacity for extracellular vesicles, including microvesicles and exosomes, to carry miRNAs that participate in cell-to-cell communication has been described. In the present study, the miRNA expression patterns for three kinds of pleural effusions that were obtained from patie...
Source: Tumor Biology - October 13, 2016 Category: Cancer & Oncology Source Type: research
Snail-activated long non-coding RNA PCA3 up-regulates PRKD3 expression by miR-1261 sponging, thereby promotes invasion and migration of prostate cancer cells
AbstractRapidly accumulated evidence has shown that long non-coding RNA (lncRNAs) disregulation is involved in human tumorigenesis in many cancers, including prostate cancer (PCa). LncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs could be valuable biomarkers and therapeutic targets. Prostate cancer antigen 3 (PCA3), also known as differential display code 3 (DD3), is one such lncRNA that maps to chromosome 9q21 –22. PCA3 expression is highly specific to PCa. In the present study, the level of PCA3 expression in prostate cancer...
Source: Tumor Biology - October 13, 2016 Category: Cancer & Oncology Source Type: research
Effects and mechanisms of action of SARI on androgen-independent prostate cancer (DU145) cells
This study aimed to characterize the role and mechanisms of action of suppressor of AP-1, regulated by IFN (SARI) in androgen-independent prostate cancer cells using the DU145 cell line. Prostate cancer cell lines were transfected to permit both the overexpression and inhibition of SARI. MTT assays and Transwell assays were performed to detect the effects of SARI overexpression and inhibition on the proliferation activity, invasiveness, and metastatic ability of DU145 cells. Expression of vascular endothelial growth factor (VEGF) and tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was m...
Source: Tumor Biology - October 13, 2016 Category: Cancer & Oncology Source Type: research
Notch3 negatively regulates chemoresistance in breast cancers
AbstractTo define the role of the NOTCH signaling pathway in the development of chemoresistance and the associated epithelial –mesenchymal transition (EMT), we investigated the effect of Notch3 on adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM cells). We found that Notch3 was downregulated and involved in the chemoresistance of MCF-7/ADM cells, while forced expression of Notch3 reversed the chemoresistan ce. Furthermore, fos-related antigen 1 (Fra1) was negatively regulated by Notch3 and was highly expressed in MCF-7/ADM cells. Increased Fra1 activated the EMT process. Finally, Notch3 expression was conf...
Source: Tumor Biology - October 13, 2016 Category: Cancer & Oncology Source Type: research
HCRP1 is downregulated in non-small cell lung cancer and regulates proliferation, invasion, and drug resistance
In conclusion, the present study demonstrate that HCRP1 is downregulated in NSCLC and regulates proliferation, invasion, and drug resistance through modulation of EGFR signaling. (Source: Tumor Biology)
Source: Tumor Biology - October 12, 2016 Category: Cancer & Oncology Source Type: research
MicroRNA-153 inhibits tumor progression in esophageal squamous cell carcinoma by targeting SNAI1
The objective of the current study was to determine ifSNAI1 expression in esophageal squamous cell carcinoma (ESCC) is regulated by miR-153. Metagenomic analysis of The Cancer Genome Atlas (TCGA) data identified an inverse correlation between miR-153 andSNAI1 expression in ESCC. Our study showed that the expression of miR-153 was noticeably downregulated in the ESCC cell line investigated and tissues, compared with normal esophageal epithelial cells and matched adjacent non-tumorous esophageal tissue. We demonstrated that miR-153 downregulated Snail expression by directly targeting the 3 ′-untranslated region (3′UTR) o...
Source: Tumor Biology - October 12, 2016 Category: Cancer & Oncology Source Type: research
Clinical application of protein induced by vitamin K antagonist-II as a biomarker in hepatocellular carcinoma
AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II) is an effective serum biomarker for HCC diagnosis and prognosis. Combined with another serum biomarker α-fetoprotein (AFP), the sensitivity and specificity of HCC diagnosis can be improved to a maximum of 94 and 98.5 %, respectively. PIVKA-II alone or in combination with AFP and/or AFP-L3 was effective in predicting the treatment response and clinical outcome of curative hepatic resection, chemothe rapy, targeted therapy, radiotherapy, ...
Source: Tumor Biology - October 12, 2016 Category: Cancer & Oncology Source Type: research
An indispensable role of CPT-1a to survive cancer cells during energy stress through rewiring cancer metabolism
In this study, we investigated the functional roles of fatty acid oxidation key enzyme carnitine palmitoyl transferase 1a (CPT-1a), during the metabolic programming of pancreatic ductal adenocarcinoma (PDAC) cells induced by glucose deprivation. Knockdown of CPT-1a decreased the intracellular nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) generation, increased reactive oxygen species (ROS) production, and induced sensitivity to glucose deprivation, whereas upregulation of CPT-1a increased the intracellular ATP required for cell survival. Further investigation showed that CPT-1a inhibitor etomoxir...
Source: Tumor Biology - October 12, 2016 Category: Cancer & Oncology Source Type: research
Prognostic risk factors in patients with bone metastasis from colorectal cancer
AbstractThe morbidity of bone metastasis (BM) from colorectal cancer (CRC) is increasing more than ever; however, insufficient research on BM from CRC leads to reduced awareness of the issue. Therefore, the aim of this study was to evaluate the clinical features and prognostic risk factors of CRC patients with BM. Clinical data were retrospectively analyzed for a total of 242 CRC patients with BM. Of the 242 CRC patients with BM, 52 (21.5 %) had bone metastasis alone (BMA) and 190 (78.5 %) had both bone and visceral metastasis (BM&VM). The median survival time (MST) after the diagnosis of BM in all 242 patients was ...
Source: Tumor Biology - October 11, 2016 Category: Cancer & Oncology Source Type: research
Ski modulate the characteristics of pancreatic cancer stem cells via regulating sonic hedgehog signaling pathway
The objectives of this study were to investigate the role of Ski in modulating pancreatic CSCs and to examine the molecular mechanisms involved in pancreatic cancer treatment both in vivo and in vitro. In in vitro study, the results showed that enhanced Ski expression could increase the expression of pluripotency maintaining markers, such as CD24, CD44, Sox-2, and Oct-4, and also components of Shh signaling pathway, such as Shh, Ptch-1, Smo, Gli-1, and Gli-2, whereas depletion of Ski to the contrary. Then, we investigated the underlying mechanism and found that inhibiting Gli-2 expression by short interfering RNA (siRNA) c...
Source: Tumor Biology - October 11, 2016 Category: Cancer & Oncology Source Type: research
Involvement of microRNAs in HER2 signaling and trastuzumab treatment
AbstractThe prognostic value of HER2 has been demonstrated in many human cancer types such us breast cancer, gastric cancer and ovarian cancer. Trastuzumab is the first anti-HER2 monoclonal antibody that has remarkably improved outcomes of patients with HER2-positive breast cancer. For HER2-positive metastatic gastric cancers, the addition of trastuzumab to traditional chemotherapy also significantly prolonged overall survival. However, intrinsic and acquired resistance to trastuzumab is common and results in disease progression. HER2 signaling network and mechanisms underlying the resistance have been broadly investigated...
Source: Tumor Biology - October 11, 2016 Category: Cancer & Oncology Source Type: research
