Epithelial‐mesenchymal transition as a fundamental mechanism underlying the cancer phenotype

Abstract

Epithelial-mesenchymal transition (EMT) is a complex process involved in embryonic development, wound healing and carcinogenesis. During this process, epithelial cells lose their defining characteristics and acquire mesenchymal properties: loss of cell-cell adhesion; increased motility and invasiveness; resistance to apoptosis and changes in cellular morphology. EMT has been implicated as a driver of metastasis and tumour invasion, as this process allows cells to detach from their niche and migrate through blood and lymphatic vessels to invade different organs. This transition involves a diverse range of transcription factors, including Twist, Snail and ZEB1, and downstream transcriptional targets, including E-cadherin, β-catenin, fibronectin and vimentin. Recent evidence indicates that cancer stem cells are required for metastatic tumours to become established at a distant site, and that cancer cells undergoing EMT may develop stem-cell characteristics as well as increased invasive potential. The role of EMT in cancer biology is newly emerging in the human field, and to date very little has been done in veterinary medicine. EMT may therefore be an important molecular determinant of tumour metastasis, and further understanding of this process may lead to novel drug targets to be exploited in both veterinary and human medicine.

Downregulated connexin32 promotes EMT through the Wnt/β-catenin pathway by targeting Snail expression in hepatocellular carcinoma

“…EMT is an important basis for obtaining the malignant phenotype of hepatocytes (4). Moreover, Cx-mediated GJ has recently been proposed to serve as an intercellular glue to suppress EMT and cancer metastasis (9), we thus explored the role of EMT in Cx32-mediated function.…”

“…During this process, cells lose polarity, cell-cell adhesion, epithelial markers such as E-cadherin, and acquire mesenchymal properties with high expression of mesenchymal molecular markers including vimentin, Snail, Slug and Twist (4). A number of studies have shown that EMT plays a crucial role in liver cancer invasion and metastasis (5–7), nevertheless, there is a lack of clear picture in HCC of the overall EMT signaling network.…”

Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue

“…2a, b). The loss of E-cadherin signifies a reduction in cell-cell adhesion and a shift of the prostate luminal cells from a clearly differentiated epithelial to a more mesenchymal phenotype and also an early stage of transformation [33, 34]. The disrupted expression of basal cell marker p63 in the prostate gland from the pbIL-6 mice also signifies the early transformation events of the prostate [35, 36] (Fig.…”

“…Activation of IGF signaling axis has been shown to play an essential role in tumor cell survival and proliferation [33]. In pbIL-6 mice, a significantly increased expression IGF-I and IGF-II was demonstrated by quantitative RT-PCR (Fig.…”

Protein kinase C-dependent regulation of human hepatic drug transporter expression

“…In addition, PMA exposure resulted in decreased mRNA expression of E-cadherin and enhanced mRNA expression of vimentin (Fig. 7B), that 14 also represent key hall-marks of EMT [40]. Reduced expression of E-cadherin protein concomitantly occurred in response to PMA, as demonstrated by Western-blotting (Fig.…”