Epithelial-Mesenchymal Transition in tumor microenvironment

Jing, Yingying; Han, Zhipeng; Zhang, Shanshan; Liu, Yan; Wei, Lixin

doi:10.1186/2045-3701-1-29

Cited by 234 publications

(206 citation statements)

References 66 publications

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“…Indeed, it was shown that epithelial ovarian cancer cells could directly induce a CAF phenotype (i.e., changes of normal fibroblasts into CAFs) via secretion of transforming growth factor β (Casey et al 2008;Iwatsuki et al 2010). At the same time, CAFs may secrete growth factors such as hepatocyte growth factor to promote cancer cell proliferation and invasion (Jing et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment–associated modifications of alternative splicing

Brosseau

Lucier

Nwilati

et al. 2013

RNA

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Pre-mRNA alternative splicing is modified in cancer, but the origin and specificity of these changes remain unclear. Here, we probed ovarian tumors to identify cancer-associated splicing isoforms and define the mechanism by which splicing is modified in cancer cells. Using high-throughput quantitative PCR, we monitored the expression of splice variants in laser-dissected tissues from ovarian tumors. Surprisingly, changes in alternative splicing were not limited to the tumor tissues but were also found in the tumor microenvironment. Changes in the tumor-associated splicing events were found to be regulated by splicing factors that are differentially expressed in cancer tissues. Overall, ∼20% of the alternative splicing events affected by the down-regulation of the splicing factors QKI and RBFOX2 were altered in the microenvironment of ovarian tumors. Together, our results indicate that the tumor microenvironment undergoes specific changes in alternative splicing orchestrated by a limited number of splicing factors.

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Section: Introductionmentioning

confidence: 99%

Tumor microenvironment–associated modifications of alternative splicing

Brosseau

Lucier

Nwilati

et al. 2013

RNA

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“…Disruption of cell-matrix attachment is a hallmark feature of most carcinomas (8). In these cancers, cells within epithelial structures, e.g., mammary acini and ducts, proliferate abnormally, lose cell-cell contact, and detach from the subjacent basal lamina to initiate migration and invasion into the surrounding stroma and subsequently metastasize to distant sites, that is, undergo an epithelial-mesenchymal transition (10,12,39). For many years, there has been great interest in understanding the nature of cell-ECM interactions in relation to tumor formation and progression (5).…”

mentioning

confidence: 99%

Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells

Blackstone

Ackerman

et al. 2015

American Journal of Physiology-Cell Physiology

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Blackstone BN, Li R, Ackerman WE 4th, Ghadiali SN, Powell HM, Kniss DA. Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells. Am J Physiol Cell Physiol 308: C642-C649, 2015. First published January 28, 2015; doi:10.1152/ajpcell.00276.2014.-Breast cancer is the second leading cause of malignant death among women. A crucial feature of metastatic cancers is their propensity to lose adhesion to the underlying basement membrane as they transition to a motile phenotype and invade surrounding tissue. Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins. Focal adhesion kinase (FAK) is pivotal for the organization of focal contacts and maturation into focal adhesions, and disruption of this process is a hallmark of early cancer invasive potential. Our recent work has revealed that myoferlin (MYOF) mediates breast tumor cell motility and invasive phenotype.In this study we demonstrate that noninvasive breast cancer cell lines exhibit increased cell-substrate adhesion and that silencing of MYOF using RNAi in the highly invasive human breast cancer cell line MDA-MB-231 also enhances cell-substrate adhesion. In addition, we detected elevated tyrosine phosphorylation of FAK (FAK Y397 ) and paxillin (PAX Y118 ), markers of focal adhesion protein activation. Morphometric analysis of PAX expression revealed that RNAi-mediated depletion of MYOF resulted in larger, more elongated focal adhesions, in contrast to cells transduced with a control virus (MDA-231 LVC cells), which exhibited smaller focal contacts. Finally, MYOF silencing in MDA-MB-231 cells exhibited a more elaborate ventral cytoskeletal structure near focal adhesions, typified by pronounced actin stress fibers. These data support the hypothesis that MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells. myoferlin; breast cancer; cell adhesion; cell motility; cell mechanics CELL-SUBSTRATUM AND CELL-CELL adhesion is a fundamental biological process required for the development and function of metazoans. Adhesion of cells to their underlying extracellular matrix (ECM) is mediated largely by integrins acting as specific receptors for proteins in the basal lamina, e.g., collagen IV, fibronection, and laminin (1, 31). Integrin engagement activates a cascade of phosphorylation events in a number of adhesion proteins, culminating in strengthening of attachment forces through the actin cytoskeleton (18,21,31). Disruption of cell-matrix attachment is a hallmark feature of most carcinomas (8). In these cancers, cells within epithelial structures, e.g., mammary acini and ducts, proliferate abnormally, lose cell-cell contact, and detach from the subjacent basal lamina to initiate migration and invasion into the surrounding stroma and subsequently metastasize to distant sites, ...

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“…The tumor microenvironment is composed of inflammatory and immune cells, hypoxia, stromal, extracellular components including extracellular matrix (ECM), as well as soluble factors, and plays an important role in facilitating cancer progression and metastasis (Jing et al, 2011). Tumor cell growth requires an increase in local vasculature to provide metabolites and oxygen.…”

Section: Defining Epithelial-mesenchymal Transition (Emt) and Emt In mentioning

confidence: 99%

Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

Zhu¹,

Gao²,

Wu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

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Epithelial-Mesenchymal Transition in tumor microenvironment

Cited by 234 publications

References 66 publications

Tumor microenvironment–associated modifications of alternative splicing

Tumor microenvironment–associated modifications of alternative splicing

Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells

Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

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