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

Abstract

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.

An Epigenetic Mechanism Underlying Doxorubicin Induced EMT in the Human BGC-823 Gastric Cancer Cell

“…The epithelial to mesenchymal transition (EMT) phenotype is characterized by the loss of cell-to-cell adhesion with the disintegration of tight, adherens, and gap junctions and a phenotypic change from an ''epithelial'' morphology to a motile, fibroblast-like morphology (Zhu et al, 2013). Originally defined as a fundamental process governing morphogenesis in multicellular organisms, EMT seems to play an important role in tumor progression, metastasis and drug resistance in diverse solid tumors (Yang and Weinberg, 2008;Kim et al, 2013).…”

GRP78 Secreted by Colon Cancer Cells Facilitates Cell Proliferation via PI3K/Akt Signaling

“…Although the mortality rate declines in the past few years, colorectal cancer (CRC) remains the third most common malignancy and a major health problem worldwide (Zhu et al, 2013). Though many risk factors have been reported to be related to the CRC occurrence, the detailed pathogenesis mechanism of CRC remains not fully understood.…”

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model

“…Increased epithelial-mesenchymal transition is associated with an increased incidence of cancer, as well as a greater potential for metastasis (26)(27)(28). The extent of EMT occurrence can be determined by measurement of proteins that are associated with the process.…”