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colon cancer, EMT

Min Zhou, Xinjian Liu, Zonghai Li, Qian Huang, Fang Li, Chuan-Yuan Li
Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 also has non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remains to be defined clearly. In this study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology...
March 10, 2018: International Journal of Cancer. Journal International du Cancer
Dimitrios Tsoumas, Sofia Nikou, Efstathia Giannopoulou, Spyridon Champeris Tsaniras, Chaido Sirinian, Ioannis Maroulis, Stavros Taraviras, Vassiliki Zolota, Haralabos P Kalofonos, Vasiliki Bravou
BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers. PATIENTS AND METHODS: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples. We also generated colon cancer cells resistant to 5-FU and oxaliplatin and studied the effect of ILK inhibition on drug response by MTT assay and on EMT and CSC markers' expression...
March 2018: Cancer Genomics & Proteomics
Nicolas Aznar, Jason Ear, Ying Dunkel, Nina Sun, Kendall Satterfield, Fang He, Nicholas A Kalogriopoulos, Inmaculada Lopez-Sanchez, Majid Ghassemian, Debashis Sahoo, Irina Kufareva, Pradipta Ghosh
Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor tyrosine kinases (RTKs), and heterotrimeric G proteins and associated GPCRs. Daple is a guanine nucleotide exchange factor (GEF) for the G protein Gαi Daple also binds to FZD and the Wnt/FZD mediator Dishevelled (Dvl), and it enhances β-catenin-independent Wnt signaling in response to Wnt5a-FZD7 signaling...
February 27, 2018: Science Signaling
Dongdong Sun, Weixing Shen, Feng Zhang, Huisen Fan, Changliang Xu, Liu Li, Jiani Tan, Yunjie Miao, Haibin Zhang, Ye Yang, Haibo Cheng
Colon cancer is the third most frequently diagnosed malignancy and has high morbidity worldwide. Epithelial-mesenchymal transition (EMT) has been increasingly implicated in colon cancer progression and metastasis. The present study was aimed to evaluate the potential antitumor activity of α-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, in human SW620 colon cancer cells stimulated with interleukin 6 (IL-6) for mimicking the tumor inflammatory microenvironment in vivo. Cell viability assay showed that IL-6 at 6...
February 22, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yun Zhu, Cindy Wang, Scott A Becker, Katie Hurst, Lourdes M Nogueira, Victoria J Findlay, E Ramsay Camp
Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Yoko Fujii-Nishimura, Ken Yamazaki, Yohei Masugi, Junya Douguchi, Yutaka Kurebayashi, Naoto Kubota, Hidenori Ojima, Minoru Kitago, Masahiro Shinoda, Akinori Hashiguchi, Michiie Sakamoto
Epithelial-mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse process, mesenchymal-epithelial transition (MET), for PDAC remains unclear. We aimed to characterize the histological finding "focal differentiation" in PDAC at perineural invasion sites in the context of MET and to investigate the role of Schwann cells in inducing tumor MET. Tumor differentiation and immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural invasion sites were examined in 168 PDAC tissues...
February 19, 2018: Pathology International
Feng Ye, Yixing Chen, Lu Xia, Jiabian Lian, Shuyu Yang
There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues...
February 14, 2018: Biochemical and Biophysical Research Communications
E Nigro, P Schettino, R Polito, O Scudiero, M L Monaco, G D De Palma, A Daniele
Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic and anti-inflammatory properties. Colorectal cancer is among the most common cancers worldwide. The aim of present study was to explore the effects of Acrp30 on both CaCo-2 and HCT116 colorectal cancer cells in terms of viability, oxidative stress, and apoptosis. In addition, since colorectal cancer represents a typical inflammation-related cancer, we investigated whether Acrp30 treatment modifies the migration and the expression of crucial proteins in the EMT transition...
February 14, 2018: Molecular and Cellular Biochemistry
Ewelina Dondajewska, Wojciech Juzwa, Andrzej Mackiewicz, Hanna Dams-Kozlowska
An intensive investigation of the development of in vitro models to study tumor biology has led to the generation of various three-dimensional (3D) culture methods that better mimic in vivo conditions. The tumor microenvironment (TME) is shaped by direct interactions among cancer cells, cancer-associated cells and the extracellular matrix (ECM). Recognizing the need to incorporate both tissue dimensionality and the heterogeneity of cells, we have developed a 3D breast cancer model. NIH3T3 fibroblasts and EMT6 breast cancer cell lines were seeded in various ratios onto a silk fibroin scaffold...
January 12, 2018: Oncotarget
Beidi Wang, Meimei Liu, Rujin Zhuang, Jing Jiang, Jiayin Gao, Hao Wang, He Chen, Zongfeng Zhang, Ye Kuang, Peiling Li
Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is dysregulated in a variety of types of human cancer. However, the role of CCAT2 in epithelial ovarian carcinoma (EOC) remains largely unknown. The aim of this study is to investigate the effect of CCAT2 on epithelial-mesenchymal transition (EMT) and related molecular mechanisms in epithelial ovarian cancer cells. In the current paper, we found that CCAT2 was significantly upregulated in EOC SKOV3, A2780 and HO8910 cell lines compared with the normal ovarian epithelial HUM-CELL-0088 cell line...
March 2018: Oncology Letters
Xiaofei Ning, Cong Wang, Meng Zhang, Kecheng Wang
Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT) is a crucial step in tumor progression and also involves in the acquisition of stem cell-like properties. Some miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here, we investigated the role of miR-147 in the regulation of stem cell-like traits of colon cancer cells. We observed that miR-147 was down-regulated in several colon cancer cell lines and overexpressed miR-147 decreased the expression of cancer stem cell (CSC) markers OCT4, SOX2 and NANOG in colon cancer cells (HCT116, SW480)...
February 9, 2018: Oncology Research
Mengmeng Zhang, Fei Miao, Rong Huang, Wenjie Liu, Yuechao Zhao, Tao Jiao, Yalan Lu, Fan Wu, Xiaojuan Wang, Han Wang, Hong Zhao, Hongge Ju, Shiying Miao, Linfang Wang, Wei Song
BACKGROUND: 40-50% of colorectal cancer (CRC) patients develop metastatic disease; the presence of metastasis hinders the effective treatment of cancer through surgery, chemotherapy and radiotherapy, which makes 5-year survival rate extremely low; therefore, studying CRC metastasis is crucial for disease therapy. In the present study, we investigated the role of rhomboid domain containing 1 (RHBDD1) in tumor metastasis of CRC. METHODS: The expression of RHBDD1 was analyzed in 539 colorectal tumor tissues for its correlation with lymphatic metastasis and distal metastasis...
February 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
Chunhong Zhang, Yangjie Xu, Haowen Wang, Gang Li, Han Yan, Zhenghua Fei, Yunsheng Xu, Wenfeng Li
The objective of this study was to investigate the effect and the mechanism by which curcumin reverses irinotecan-induced chemotherapy resistance in colon cancer. Construction of irinotecan-resistant colon cancer model LoVo/CPT-11R cells was performed by increasing drug concentration. The Cell Counting Kit-8 assay was used to detect inhibition of proliferation; cell morphology was observed by an optical microscope. Quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial-mesenchymal transition (EMT); drug-resistant cells were treated with curcumin at different concentrations and Cell Counting Kit-8 was reperformed to detect cell proliferation after treatments...
February 7, 2018: Anti-cancer Drugs
Zhiyao Xu, Jingjing Tao, Ping Chen, Long Chen, Sherven Sharma, Guanyu Wang, Qinghua Dong
SCOPE: Short chain fatty acid sodium butyrate (NaB) is the byproduct of bacterial anaerobic fermentation of dietary fiber in the colon, and has been shown to have an anti-tumor effect on colorectal cancer (CRC). The miR-200 family is a key regulator of the epithelial-mesenchymal transition (EMT). We investigated the role of miR-200s expression on cell migration in NaB treated CRC cells. METHODS AND RESULTS: HCT116 and LOVO CRC cells treated with NaB depicted reduced cell proliferation, enhanced apoptosis and cell cycle arrest...
February 8, 2018: Molecular Nutrition & Food Research
Sebastian Lamprecht, Markus Kaller, Eva Marina Schmidt, Cristina Blaj, Tobias S Schiergens, Jutta Engel, Andreas Jung, Heiko Hermeking, Thomas G P Grünewald, Thomas Kirchner, David Horst
Purpose: Colorectal cancers are composed of phenotypically different tumor cell subpopulations within the same core genetic background. Here, we identify high expression of the TALE transcription factor PBX3 in tumor cells undergoing epithelial-mesenchymal transition (EMT), analyze PBX3 regulation, and determine clinical associations in colorectal cancer. Experimental design: We used transcriptomic and in situ analyses to identify PBX3 expression in colorectal cancer and cell biology approaches to determine its regulation and function...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shani Ben Harosh-Davidovich, Isam Khalaila
O-GlcNAcylation, the addition of β-N-acetylglucosamine (O-GlcNAc) moiety to Ser/Thr residues, is a sensor of the cell metabolic state. Cancer diseases such as colon, lung and breast cancer, possess deregulated O-GlcNAcylation. Studies during the last decade revealed that O-GlcNAcylation is implicated in cancer tumorigenesis and proliferation. The Wnt/β-catenin signaling pathway and cadherin-mediated adhesion are also implicated in epithelial-mesenchymal transition (EMT), a key cellular process in invasion and cancer metastasis...
January 30, 2018: Experimental Cell Research
Stephen J O'Brien, Jane V Carter, James F Burton, Brent G Oxford, Miranda N Schmidt, Jacob C Hallion, Susan Galandiuk
Colorectal cancer is associated with significant morbidity and mortality as many patients are diagnosed with advanced stage disease. MicroRNAs are small, non-coding RNA molecules which have a major role in gene expression regulation and are dysregulated in colorectal cancer. The miR-200 family is involved in epithelial-to-mesenchymal transition (EMT). This systematic review describes the roles of the miR-200 family in EMT in colorectal cancer. A search of electronic databases (PubMed and Embase) was conducted between January 2000 and July 2017...
January 31, 2018: International Journal of Cancer. Journal International du Cancer
Shinji Osada, Ayana Gotoh, Ryoma Yokoi, Hiroshi Tsuchiya, Takuji Sakuratani, Yoshiyuki Sasaki, Naoki Okumura, Hideki Hayashi, Tsuyoshi Mukai
BACKGROUND/AIM: The aim of the present study was to further develop our previous study on c-Met expression in colorectal cancer and epithelial-mesenchymal transition (EMT) induced by hepatocyte growth factor (HGF), to investigate EMT in the process of liver metastases, and evaluate the effects of chemotherapy on EMT cells as a therapeutic strategy for colorectal liver metastasis. MATERIALS AND METHODS: CT26 colon cancer cells were treated with 5-FU and oxaliplatin with or without HGF...
February 2018: Anticancer Research
Arseniy E Yuzhalin, Tomas Urbonas, Michael A Silva, Ruth J Muschel, Alex N Gordon-Weeks
BACKGROUND: Accumulating evidence implicates the tumour stroma as an important determinant of cancer progression but the protein constituents relevant for this effect are unknown. Here we utilised a bioinformatics approach to identify an extracellular matrix (ECM) gene signature overexpressed in multiple cancer types and strongly predictive of adverse outcome. METHODS: Gene expression levels in cancers were determined using Oncomine. Geneset enrichment analysis was performed using the Broad Institute desktop application...
January 23, 2018: British Journal of Cancer
Helen Aggelou, Panagiota Chadla, Sofia Nikou, Sofia Karteri, Ioannis Maroulis, Haralabos P Kalofonos, Helen Papadaki, Vasiliki Bravou
Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB...
January 19, 2018: Virchows Archiv: An International Journal of Pathology
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