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colon cancer, EMT

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https://www.readbyqxmd.com/read/28202525/oncogenic-effects-of-high-mapk-activity-in-colorectal-cancer-mark-progenitor-cells-and-persist-irrespective-of-ras-mutations
#1
Cristina Blaj, Eva Marina Schmidt, Sebastian Lamprecht, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
About 40% of colorectal cancers have mutations in KRAS accompanied by downstream activation of MAPK signaling which promotes tumor invasion and progression. Here we report that MAPK signaling shows strong intratumoral heterogeneity and unexpectedly remains regulated in colorectal cancer irrespective of KRAS mutation status. Using primary colorectal cancer tissues, xenograft models and MAPK reporter constructs, we showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition (EMT), and expressed markers related to colon cancer stem cells...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28192397/downregulation-of-mir-218-contributes-to-epithelial-mesenchymal-transition-and-tumor-metastasis-in-lung-cancer-by-targeting-slug-zeb2-signaling
#2
Z-M Shi, L Wang, H Shen, C-F Jiang, X Ge, D-M Li, Y-Y Wen, H-R Sun, M-H Pan, W Li, Y-Q Shu, L-Z Liu, S C Peiper, J He, B-H Jiang
Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28185461/-epithelial-mesenchymal-transition-in-tumor-tissue-and-its-role-for-metastatic-spread-of-cancer
#3
V M Matějka, J Fínek, M Králíčková
BACKGROUND: Metastasis, recurrence, and resistance to chemotherapy are leading causes of the majority of cancer-related mortality worldwide. The process of metastasis can be artificially divided into a series of sequential, highly organized, and organ-specific steps. The underlying mechanisms are still poorly understood, but are believed to be mediated by epithelial-mesenchymal transition (EMT). First described in embryogenesis, EMT is a cellular reprogramming process in which epithelial cells acquire a mesenchymal phenotype...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28163188/transcriptional-repression-of-mir-200-family-members-by-nanog-in-colon-cancer-cells-induces-epithelial-mesenchymal-transition-emt
#4
Qiong Pan, Linkun Meng, Jun Ye, Xiaolong Wei, Yangyang Shang, Yin Tian, Yonghong He, Zhihong Peng, Lei Chen, Wensheng Chen, Xiuwu Bian, Rongquan Wang
Nanog is an important embryonic stem cell (ESC) gene that does not function as a classical oncogene, but needs to cooperate with other molecules to potentiate tumorigenic activity. The question addressed by the present study was whether a miRNA link exists between Nanog and epithelial-mesenchymal transition (EMT)-mesenchymal-epithelial transition (MET) plasticity. Here, we found that Nanog mRNA expression level was inversely correlated with miR-200c and miR-200b expression levels in colon cancer cell lines and human colorectal cancer tissues...
February 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28130225/cellular-model-of-colon-cancer-progression-reveals-signatures-of-mrnas-mirna-lncrnas-and-epigenetic-modifications-associated-with-metastasis
#5
Matjaz Rokavec, David Horst, Heiko Hermeking
Here we developed and comprehensively characterized a cellular model of colon cancer progression consisting of four defined derivatives of a colon cancer cell line that resulted from consecutive epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT/MET) and phenotypically recapitulate the metastatic cascade. Initial EMT was induced by prolonged exposure to IL-6, a cytokine also generated by the tumor-stroma. Genome-wide characterization of transcriptional (mRNA, miRNA, lncRNA) and epigenetic (DNA methylation, H3K4me3, H3K79me3, and H3K27me3 histone modifications) profiles of the cell derivatives, combined with correlative analyses of expression, methylation, and clinical data from the TCGA-COAD database gave insights into the molecular basis of their phenotypic changes...
January 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28105212/emt-influences-the-expression-of-ck19-in-pleural-effusion-derived-lung-cancer-cells-and-their-invasion-and-metastasis
#6
Dongyun Huang, Wenjing Xu, Xingxiang Xu, Xudong Zhang, Rui Zhou, Ping Chen
Lung cancer is the most common cancer after breast and colon cancer, with high rates of mortality, worldwide. There are two main types of lung cancer, small cell lung carcinoma (SCLC), which accounts for approximately 20% of all lung cancer cases and non-SCLC, which accounts for almost 80% of lung cancer cases. Although lung cancer is one of the most aggressive types of cancer, progress in achieving better clinical outcomes has been gradual. Even though a number of markers have been suggested for the diagnosis of lung cancer and monitoring of disease progression, there is no clear way of assessing the invasion, epithelial-mesenchymal transition (EMT) and metastasizing capability of the primary tumor cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104986/expression-of-trefoil-factors-and-twist1-in-colorectal-cancer-and-their-correlation-with-metastatic-potential-and-prognosis
#7
Akram Yusup, Bailikezi Huji, Cheng Fang, Fei Wang, Tuerxunjiang Dadihan, Hai-Jiang Wang, Halmurat Upur
AIM: To detect the expression of trefoil factors (TFFs) and TWIST1 in colorectal cancer (CRC) and analyze their correlation with metastasis and survival. METHODS: This study examined the expression of TFF1, TFF3 and TWIST1 in a total of 75 tumor samples, 47 matched normal samples (15 cm from the lesion margin), 30 metastatic lymph nodes, and 10 liver metastatic cancer samples from patients with CRC. The relationship was then analyzed between the protein expression and different clinical records...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28098885/carboxamide-analog-itr-284-evokes-apoptosis-and-inhibits-migration-ability-in-human-lung-adenocarcinoma-a549-cells
#8
Jai-Sing Yang, Chia-An Lin, Chi-Cheng Lu, Yen-Fang Wen, Fuu-Jen Tsai, Shih-Chang Tsai
Lung adenocarcinoma is the most common type of lung cancer and found in both smokers and non-smokers, but the treatment of lung cancer is limited. ITR-284 has been shown to be a potent carboxamide-derived anticancer agent and to induce apoptosis in leukemia and colon cancer cells. However, little is known whether ITR-284 has anticancer activity in human lung adenocarcinoma cells through induction of apoptosis and suppression of migration in vitro. We showed that ITR-284 inhibited human lung cancer A549 cells using the thiazolyl blue tetrazolium bromide (MTT) assay and evoked apoptosis via the cell cycle distribution at S phase arrest...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098359/m2-like-macrophages-induce-colon-cancer-cell-invasion-via-matrix-metalloproteinases
#9
Katyayni Vinnakota, Yuan Zhang, Benson Chellakkan Selvanesan, Geriolda Topi, Tavga Salim, Janna Sand-Dejmek, Gunilla Jönsson, Anita Sjölander
The inflammatory milieu plays an important role in colon cancer development and progression. Previously, we have shown that tumor-associated macrophages (TAMs), an important component of the tumor microenvironment, are enriched in tumors compared with normal tissue and confer a poorer prognosis. In the present study, we found that matrix metallopeptidase-9 (MMP-9), which degrades extracellular matrix proteins, was increased in biopsies from colon cancer patients and in mouse xenografts with SW480 cell-derived tumors...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28093285/the-depletion-of-atm-inhibits-colon-cancer-proliferation-and-migration-via-b56%C3%AE-2-mediated-chk1-p53-cd44-cascades
#10
Rui Liu, Jiajia Tang, Chaodong Ding, Weicheng Liang, Li Zhang, Tianke Chen, Yan Xiong, Xiaowei Dai, Wenfeng Li, Yunsheng Xu, Jin Hu, Liting Lu, Wanqin Liao, Xincheng Lu
Ataxia-telangiectasia mutated (ATM) protein kinase is a major guardian of genomic stability, and its well-established function in cancer is tumor suppression. Here, we report an oncogenic role of ATM. Using two isogenic sets of human colon cancer cell lines that differed only in their ATM status, we demonstrated that ATM deficiency significantly inhibits cancer cell proliferation, migration, and invasion. The tumor-suppressive function of ATM depletion is not modulated by the compensatory activation of ATR, but it is associated with B56γ2-mediated Chk1/p53/CD44 signaling pathways...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#11
Steffi Lehmann, Veronika Te Boekhorst, Julia Odenthal, Roberta Bianchi, Sjoerd van Helvert, Kristian Ikenberg, Olga Ilina, Szymon Stoma, Jael Xandry, Liying Jiang, Reidar Grenman, Markus Rudin, Peter Friedl
Cancer metastases arise from a multi-step process that requires metastasizing tumor cells to adapt to signaling input from varying tissue environments [1]. As an early metastatic event, cancer cell dissemination occurs through different migration programs, including multicellular, collective, and single-cell mesenchymal or amoeboid migration [2-4]. Migration modes can interconvert based on changes in cell adhesion, cytoskeletal mechanotransduction [5], and/or proteolysis [6], most likely under the control of transcriptional programs such as the epithelial-to-mesenchymal transition (EMT) [7, 8]...
February 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28075454/expression-of-glia-maturation-factor-%C3%AE-is-associated-with-colorectal-cancer-metastasis-and-its-downregulation-suppresses-colorectal-cancer-cell-migration-and-invasion-in-vitro
#12
Huili Wang, Zhijiang Chen, Hongen Chang, Xiaoping Mu, Wenyu Deng, Zhaohu Yuan, Fang Yao, Yan Liu, Rongjia Mai, Bingyi Wu
Glia maturation factor γ (GMFG) functions to reorganize the actin cytoskeleton and appears to play a causative role in cell migration and adherence. The present study assessed GMFG expression in colorectal cancer cells and tissue specimens and then explored the role of GMFG in colorectal cancer progression in vitro. GMFG protein was highly expressed in colorectal cancer tissues and a metastatic colon cancer cell line. Knockdown of GMFG expression using GMFG siRNA or anti-GMFG antibody decreased the capacity of colon cancer LoVo cell migration and invasion in vitro, while recombinant GMFG treatment induced LoVo cell migration...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28068625/loss-of-periplakin-expression-is-associated-with-the-tumorigenesis-of-colorectal-carcinoma
#13
Xiang Li, Guohui Zhang, Yan Wang, Ahmed Elgehama, Yang Sun, Lele Li, Yanhong Gu, Wenjie Guo, Qiang Xu
Periplakin (PPL), a member of the plakin protein family, has been reported to be down-expressed in urothelial carcinoma. The role of PPL in human colorectal cancer, however, remains largely unknown. Also little is known about the contribution of PPL to the malignant property of colorectal cancer and the intracellular function of PPL. In this study, we demonstrated that PPL was apparently down-expressed in colon carcinomas compared with normal and para-carcinoma tissues, which was correlated with the tumor size...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28061476/mir-675-5p-supports-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colon-cancer-cells
#14
Viviana Costa, Alessia Lo Dico, Aroldo Rizzo, Francesca Rajata, Marco Tripodi, Riccardo Alessandro, Alice Conigliaro
The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1α, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1α; here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis.Our results show that miR-675-5p, over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1α induced EMT...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059830/2-deoxy-d-glucose-suppresses-the-migration-and-reverses-the-drug-resistance-of-colon-cancer-cells-through-adam-expression-regulation
#15
Ga B Park, Yoon H Chung, Daejin Kim
Cancer cell resistance to chemotherapy is associated with a poor prognosis. The compound 2-deoxy-D-glucose (2-DG) enhances the effect of chemotherapy against cancer cells lines in vitro and in vivo. However, its effect on the epithelial to mesenchymal transition (EMT) in drug-resistant cancer cells has not been fully elucidated. In this study, we investigated whether treatment of 5-fluorouracil or oxaliplatin-resistant colorectal cancer (CRC) cells with 2-DG suppressed their migratory activity and enhanced their susceptibility to chemotherapy...
January 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28056464/impact-of-ctla-4-blockade-in-conjunction-with-metronomic-chemotherapy-on-preclinical-breast-cancer-growth
#16
Karla Parra, Paloma Valenzuela, Natzidielly Lerma, Alejandra Gallegos, Luis C Reza, Georgialina Rodriguez, Urban Emmenegger, Teresa Di Desidero, Guido Bocci, Mitchell S Felder, Marian Manciu, Robert A Kirken, Giulio Francia
BACKGROUND: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated. METHODS: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg(-1) day(-1)), b) bolus (150 mg kg(-1)) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg(-1) every 3 days)...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28035402/transforming-growth-factor-%C3%AE-1-suppresses-bone-morphogenetic-protein-2-induced-mesenchymal-epithelial-transition-in-hsc-4-human-oral-squamous-cell-carcinoma-cells-via-smad1-5-9-pathway-suppression
#17
Takahiro Chiba, Akira Ishisaki, Seiko Kyakumoto, Toshiyuki Shibata, Hiroyuki Yamada, Masaharu Kamo
Squamous cell carcinoma is the most common cancer in the oral cavity. We previously demonstrated that transforming growth factor-β1 (TGF-β1) promotes the epithelial-mesenchymal transition (EMT) of human oral squamous cell carcinoma (hOSCC) cells; however, it remains to be clarified whether the TGF-β superfamily member bone morphogenetic protein (BMP) affects this process in hOSCC cells. Here, we examined the independent and collective effects of TGF-β1 and BMP-2 on EMT and mesenchymal‑epithelial transition (MET) in a panel of four hOSCC cell lines...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28032860/osteopontin-facilitates-tumor-metastasis-by-regulating-epithelial-mesenchymal-plasticity
#18
Rongjie Jia, Yingchao Liang, Rui Chen, Guoke Liu, Hao Wang, Min Tang, Xuyu Zhou, Huajing Wang, Yang Yang, Huafeng Wei, Bohua Li, Yipeng Song, Jian Zhao
Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during metastatic colonization. Unlike secretory OPN (sOPN), which triggers the epithelial-mesenchymal transition (EMT) to initiate cancer metastasis, intracellular/nuclear OPN (iOPN) induces the mesenchymal-epithelial transition (MET) to facilitate the formation of metastases...
December 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27998883/unlocking-aspirin-s-chemopreventive-activity-role-of-irreversibly-inhibiting-platelet-cyclooxygenase-1
#19
Lenard M Lichtenberger, Dexing Fang, Roger J Bick, Brian J Poindexter, Tri Phan, Angela L Bergeron, Subhashree Pradhan, Elizabeth J Dial, K Vinod Vijayan
The mechanism by which aspirin consumption is linked to significant reductions in the incidence of multiple forms of cancer and metastatic spread to distant tissues, resulting in increased cancer patient survival is not well understood. In this study, using colon cancer as an example, we provide both in vitro (cell culture) and in vivo (chemically induced mouse model of colon cancer) evidence that this profound antineoplastic action may be associated with aspirin's ability to irreversibly inhibit COX-1-mediated platelet activation, thereby blocking platelet-cancer cell interactions, which promote cancer cell number and invasive potential...
February 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/27938499/knockdown-of-long-noncoding-rna-ccat2-inhibits-cellular-proliferation-invasion-and-emt-in-glioma-cells
#20
Jing Zeng, Tianping Du, Yafeng Song, Yan Gao, Fuyan Li, Ruimin Wu, Yijia Chen, Wei Li, Hong Zhou, Yi Yang, Zhijun Pei
Long noncoding RNAs (lncRNAs) colon cancer associated transcript 2 (CCAT2) have been demonstrated as playing importantroles in diverse tumorigenesis. However, the biological function of lncRNA in glioma are still unknown. In this study,we found that lncRNA CCAT2 was overexpressed in glioma tissues and cell lines and associated with tumor grade and tumor size. Furthermore, patients with high levels of lncRNA CCAT2 had poorer survival than those with lower levels of lncRNA CCAT2. Knocking down lncRNA CCAT2 expression significantly suppressed the glioma cell growth, migration and invasion, as well as induced early apoptosis of glioma cell in vitro...
November 17, 2016: Oncology Research
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