Role of Epithelial to Mesenchymal Transition in Colorectal Cancer

Abstract

The epithelial–mesenchymal transition (EMT) is a cellular reprogramming process that occurs during embryonic development and adult tissue homeostasis. This process involves epithelial cells acquiring a mesenchymal phenotype. Through EMT, cancer cells acquire properties associated with a more aggressive phenotype. EMT and its opposite, mesenchymal–epithelial transition (MET), have been described in more tumors over the past ten years, including colorectal cancer (CRC). When EMT is activated, the expression of the epithelial marker E-cadherin is decreased and the expression of the mesenchymal marker vimentin is raised. As a result, cells temporarily take on a mesenchymal phenotype, becoming motile and promoting the spread of tumor cells. Epithelial–mesenchymal plasticity (EMP) has become a hot issue in CRC because strong inducers of EMT (such as transforming growth factor β, TGF-β) can initiate EMT and regulate metastasis, microenvironment, and immune system resistance in CRC. In this review, we take into account the significance of EMT-MET in CRC and the impact of the epithelial cells’ plasticity on the prognosis of CRC. The analysis of connection between EMT and colorectal cancer stem cells (CCSCs) will help to further clarify the current meager understandings of EMT. Recent advances affecting important EMT transcription factors and EMT and CCSCs are highlighted. We come to the conclusion that the regulatory network for EMT in CRC is complicated, with a great deal of crosstalk and alternate paths. More thorough research is required to more effectively connect the clinical management of CRC with biomarkers and targeted treatments associated with EMT.

Tumor specific TGF-β insensitive CD8 + T cells augments the antitumor effect through inhibition of epithelial-mesenchymal transition in CD 105 + renal carcinoma stem cells

“…These results indicated that TGF-β play important role in RCC and promote the EMT in CSCs, which related with recurrence and metastasis. Accumulating evidences have shown the connection between the EMT and CSCs in human cancers, and TGF-β plays pivotal role not only in the stemness of CSCs but also in the immune cells in tumor microenvironment [24][25][26]. TGF-β can control adaptive immunity by promoting the expansion of Treg cells directly, regulating the regulatory CD4 + T cell response, controlling the function of effector T cells.…”

High BAP1 expression is associated with poor prognosis in patients with colorectal liver metastases

“…During progression, cancer cells acquire a phenotypic change from epithelial to mesenchymal and exhibit aggressive behavior. This phenomenon, the so-called EMT, plays a critical role in cancer progression, metastasis, and recurrence after curative treatment for primary lesions [21,22] . Our in vitro data demonstrate that BAP1 promotes cell migration and invasion.…”

The Nexus of Inflammation-Induced Epithelial-Mesenchymal Transition and Lung Cancer Progression: A Roadmap to Pentacyclic Triterpenoid-Based Therapies

“…For example, the use of celecoxib (a selective COX-2 inhibitor) as an adjuvant to chemotherapy significantly improved the overall survival and disease-free survival in COX-2-positive gastric cancer patients [128], and its oral administration significantly improved responses in patients with recurrent ovarian cancer characterized by platinum-based drug resistance (phase II, NCT01124435) [129]. Another COX-2 inhibitor, rofecoxib, in combination with cyclophosphamide and vinblastine, showed a 30% clinical benefit in patients with advanced solid tumors [130], and low-dose aspirin prevented colorectal cancer in patients with familial adenomatous polyposis by suppressing the recurrence of colorectal polyps (UMIN000018736) [131], a process associated with EMT [132]. These results are consistent with the recent retrospective analysis by Cai et al demonstrating that the use of non-steroidal anti-inflammatory drugs during radical resection in NSCLC patients correlates with outcomes [133].…”