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colon cancer, EMT

Ajaz A Bhat, Rizwan Ahmad, SrijayaPrakash B Uppada, Amar B Singh, Punita Dhawan
Epithelial-mesenchymal transition (EMT) is an important mechanism in cancer progression and malignancy including colorectal cancer (CRC). Importantly, inflammatory mediators are critical constituents of the local tumor environment and an intimate link between CRC progression and inflammation is now validated. We and others have reported key role of the deregulated claudin-1 expression in colon carcinogenesis including colitis-associated colon cancer (CAC). However, the causal association between claudin-1 expression and inflammation-induced colon cancer progression remains unclear...
October 11, 2016: Experimental Cell Research
Bing Chen, Xiao Zeng, Yu He, Xixi Wang, Ziwei Liang, Jingjing Liu, Peng Zhang, Hongxia Zhu, Ningzhi Xu, Shufang Liang
The STC2 protein involves in carcinogenesis and progression of many cancers. It remains unclear how STC2 regulates the epithelial-mesenchymal transition (EMT) process and colorectal cancer (CRC) development. Here we systematically investigated STC2-activated early occurrence of EMT and CRC cell migration in vitro, clinical associations of STC2 with CRC development and patient survival. The secretion and expression level of STC2 were both greatly increased in EMT cells and CRC cells compared with the normal epithelial NCM460 cells...
September 20, 2016: Oncotarget
Richard Ottman, Jenna Levy, Grizzle E Williams, Ratna Chakrabarti
miR-17-92a cluster miRNAs are transcribed from a polycistronic transcription unit C13orf25 that generates six mature miRNAs, miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a that are overexpressed in lung and colon cancers. Here we show that the expression of miR-17-92a miRNAs are reduced in cancerous prostate tissues compared to uninvolved areas and also in aggressive prostate cancer cells. Restoration of expression of all members of miR-17-92a cluster showed, decreased expression of cell cycle regulatory proteins cyclin D1 and SSH1; and LIMK1 and FGD4 of RhoGTPase signaling pathway...
September 16, 2016: Oncotarget
C-C Liu, D-L Cai, F Sun, Z-H Wu, B Yue, S-L Zhao, X-S Wu, M Zhang, X-W Zhu, Z-H Peng, D-W Yan
We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and β-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae...
September 19, 2016: Oncogene
Gilles Gadea, Nikola Arsic, Kenneth Fernandes, Alexandra Diot, Sébastien M Joruiz, Samer Abdallah, Valerie Meuray, Stéphanie Vinot, Christelle Anguille, Judit Remenyi, Marie P Khoury, Philip R Quinlan, Colin A Purdie, Lee B Jordan, Frances V Fuller-Pace, Marion de Toledo, Maïlys Cren, Alastair M Thompson, Jean-Christophe Bourdon, Pierre Roux
TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of TP53 mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53...
September 15, 2016: ELife
Min Lu, Zhuo Liu, Bo Li, Gang Wang, Dechuan Li, Yuping Zhu
BACKGROUND: Long non-coding RNAs (lncRNAs) have been shown to have crucial regulatory roles in human cancer biology. LncRNA PANDAR is a novel identified lncRNA that was previously reported to be increased in various cancers; however, its effect in colorectal cancer (CRC) remains unknown. The aim of this study was to explore the expression and role of lncRNA PANDAR in CRC. METHODS: The expression of lncRNA PANDAR was examined in CRC samples and cell lines by qRT-PCR...
September 14, 2016: Journal of Cancer Research and Clinical Oncology
José M García-Heredia, Eva M Verdugo Sivianes, Antonio Lucena-Cacace, Sonia Molina-Pinelo, Amancio Carnero
NumbL, or Numb-like, is a close homologue of Numb, and is part of an evolutionary conserved protein family implicated in some important cellular processes. Numb is a protein involved in cell development, in cell adhesion and migration, in asymmetric cell division, and in targeting proteins for endocytosis and ubiquitination. NumbL exhibits some overlapping functions with Numb, but its role in tumorigenesis is not fully known. Here we showed that the downregulation of NumbL alone is sufficient to increase NICD nuclear translocation and induce Notch pathway activation...
August 23, 2016: Oncotarget
Sung-Hoon Jung, Su-Min Kim, Choong-Eun Lee
Reactive oxygen species (ROS) participate in malignant progression of cancers including epithelial-mesenchymal transition (EMT). We have investigated the role of suppressors of cytokine signaling (SOCS)1 as an inhibitor of ROS-induced EMT using colon cancer cell lines transduced with SOCS1 and shSOCS1. Hydrogen peroxide treatment induced EMT features such as elevation of vimentin and Snail with a corresponding reduction of E-cadherin. The EMT markers are significantly decreased upon SOCS1 over-expression while increased under SOCS1 knock-down...
August 23, 2016: Oncotarget
Jimin Shin, In-Sung Song, Jhang Ho Pak, Sung-Wuk Jang
Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis of epithelial cancer cells. Butyrate, which is produced from dietary fiber by colonic bacterial fermentation, has been reported to influence EMT. However, some studies have reported that butyrate promotes EMT, while others have reported an inhibitory effect. To clarify these controversial results, it is necessary to elucidate the mechanism by which butyrate can influence EMT. In this study, we examined the potential role of annexin A1 (ANXA1), which was previously reported to promote EMT in breast cancer cells, as a mediator of EMT regulation by butyrate...
September 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Elisabetta Bigagli, Cristina Luceri, Daniele Guasti, Lorenzo Cinci
Cancer-secreted exosomes influence tumor microenvironment and support cancer growth and metastasis. MiR-210 is frequently up-regulated in colorectal cancer tissues and correlates with metastatic disease. We investigated whether exosomes are actively released by HCT-8 colon cancer cells, the role of exosomal miR-210 in the cross-talk between primary cancer cells and neighboring metastatic cells and its contribution in regulating epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET)...
August 11, 2016: Cancer Biology & Therapy
Zefeng Zhang, Xiaoling Bu, Hao Chen, Qiyi Wang, Weihong Sha
Metastasis and recurrence are the challenges of cancer therapy. Recently, mounting evidence has suggested that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) are critical factors in tumor metastasis and recurrence. The oncogene, Bmi-1, promotes the development of hematologic malignancies and many solid tumors. The aim of the present study was to elucidate the mechanisms through which Bmi-1 promotes the invasion and migration of colon CSCs (CCSCs) using the HCT116 colon cancer cell line...
October 2016: International Journal of Molecular Medicine
Ga Bin Park, Yoon Hee Chung, Ji Hee Gong, Dong-Hoon Jin, Daejin Kim
Glycogen synthase kinase-3β (GSK-3β) in cancer cells is a critical regulatory component of both cellular metabolism and epithelial-mesenchymal transition (EMT) processes via regulation of the β-catenin/E-cadherin and phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Lipogenesis of cancer cells also plays a critical role in survival and metastasis. We investigated the role of GSK-3β-mediated intracellular fatty acid synthesis to control EMT in TLR4-activated colorectal cancer cells and the underlying regulatory mechanism...
September 5, 2016: International Journal of Oncology
Chueh-Lin Hsu, Feng-Hsiang Chung, Chih-Hao Chen, Tzu-Ting Hsu, Szu-Mam Liu, Dao-Sheng Chung, Ya-Fen Hsu, Chien-Lung Chen, Nianhan Ma, Hoong-Chien Lee
Cancer stem cells (CSCs), or cancer cells with stem cell-like properties, generally exhibit drug resistance and have highly potent cancer inducing capabilities. Genome-wide expression data collected at public repositories over the last few years provide excellent material for studies that can lead to insights concerning the molecular and functional characteristics of CSCs. Here, we conducted functional genomic studies of CSC based on fourteen PCA-screened high quality public CSC whole genome gene expression datasets and, as control, four high quality non-stem-like cancer cell and non-cancerous stem cell datasets from the Gene Expression Omnibus database...
2016: Scientific Reports
Martin H M Sailer, Durga Sarvepalli, Catherine Brégère, Urs Fisch, Marin Guentchev, Michael Weller, Raphael Guzman, Bernhard Bettler, Arkasubhra Ghosh, Gregor Hutter
Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood...
2016: Journal of Visualized Experiments: JoVE
Xiaomin Zhong, Lan Zheng, Jianfeng Shen, Dongmei Zhang, Minmin Xiong, Youyou Zhang, Xinhong He, Janos L Tanyi, Feng Yang, Kathleen T Montone, Xiaojun Chen, Congjian Xu, Andy P Xiang, Qihong Huang, Xiaowei Xu, Lin Zhang
Oncogenic KRAS contributes to malignant transformation, antiapoptosis, and metastasis in multiple human cancers, such as lung, colon, and pancreatic cancers and melanoma. MicroRNAs (miRNAs) are endogenous 18- to 25-nucleotide noncoding small RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or inhibition of protein translation. In the present study, using array-based miRNA profiling in IMR90 and MCF10A cells expressing oncogenic KRAS, we identified that the expression of the microRNA 200 (mir-200) family was suppressed by KRAS activation and that this suppression was mediated by the transcription factors JUN and SP1 in addition to ZEB1...
November 1, 2016: Molecular and Cellular Biology
Zhong Xiong, Meng Guo, Yun Yu, Fei-Fei Zhang, Meng-Kai Ge, Guo-Qiang Chen, Shao-Ming Shen
Recently, we have reported that apoptosis-inducing factor (AIF) regulates the epithelial-mesenchymal transition (EMT) process of cancers, but the mechanisms underlying the regulation of AIF expression in cancers remain greatly unknown. Here, we report that hypoxia inversely correlates with the expression of AIF in tumor tissues from a cohort of colon cancer patients and inhibits AIF expression in multiple colon cancer cell lines. This inhibition is mediated by hypoxia-inducible factor-1 (HIF-1), which transcriptionally represses AIF through direct binding to the hypoxia-response element in AIF promoter as revealed by luciferase reporter and chromatin immunoprecipitation assays...
August 19, 2016: Carcinogenesis
Qingguo Li, Ping Wei, Ben Huang, Ye Xu, Xinxiang Li, Yaqi Li, Sanjun Cai, Dawei Li
MAEL plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilisation, however, its role on cancers is unclear. In this study, MAEL expression was analysed in a tissue microarray containing 185 samples of primary colon cancer tumor samples and human colon cancer cell lines. The effect of MAEL on cell proliferation, tumorigenesis, metastasis and drug resistance was examined in vitro and in vivo. Immunoprecipitation assay, confocal immunofluorescent analysis and luciferase assay were used for mechanism study...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
W Zhou, M G Cao, J Xu, Z Y Fang, X Y Wang, Z P Guo, S S Li, Z H Zhou
OBJECTIVE: To investigate the effect of GTPase activating protein Git2 on metastasis in breast cancer. METHODS: Git2 gene over-expression was induced by Git2 cDNA, and Git2 gene knockdown was induced by Git2 ShRNA lentivirus in four breast cancer cell lines. Six-week old wide type female mice were also used in this study. The cells were tagged with luciferase and injected into wide type female mice by tail vein or 4(th) mammary fat pad, respectively, to establish a cancer metastasis model...
July 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Salman B Hosain, Sachin K Khiste, Mohammad B Uddin, Vindya Vorubindi, Catherine Ingram, Sifang Zhang, Ronald A Hill, Xin Gu, Yong-Yu Liu
Missense mutation of tumor suppressor p53, which exhibits oncogenic gain-of-function (GOF), not only promotes tumor progression, but also diminishes therapeutic efficacies of cancer treatments. However, it remains unclear how a p53 missense mutant contributes to induced pluripotency of cancer stem cells (CSCs) in tumors exposed to chemotherapeutic agents. More importantly, it may be possible to abrogate the GOF by restoring wild-type p53 activity, thereby overcoming the deleterious effects resulting from heterotetramer formation, which often compromises the efficacies of current approaches being used to reactivate p53 function...
August 10, 2016: Oncotarget
Yu-Jia Chang, Ya-Wen Cheng, Ruo-Kai Lin, Chi-Chou Huang, William Tzu-Liang Chen, Tao-Wei Ke, Po-Li Wei
BACKGROUND: Treatment resistance and metastasis are the major causes of death among patients with colorectal cancer (CRC). Approximately 20% of surgically treated patients ultimately develop metastases during the follow-up period. Currently, the TNM system is the only available prognostic test. Therefore, the identification of new markers for CRC remains important. Thrombomodulin (TM), a glycoprotein, is involved in angiogenesis and has been linked to many malignant diseases. However, the function of TM in CRC remains unclear...
2016: PloS One
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