Abstract
Epithelial to mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, for instance cell polarity and cell–cell contact, and gain mesenchymal properties, such as increased motility. In colorectal cancer (CRC), EMT is associated with an invasive or metastatic phenotype. In this review, we discuss recent studies exploring novel regulation mechanisms of EMT in CRC, including the identification of new CRC EMT regulators. Upregulation of inducers can promote EMT, leading to increased invasiveness and metastasis in CRC. These inducers can downregulate E-cadherin and upregulate N-cadherin and vimentin (VIM) through modulating EMT-related signaling pathways, for instance WNT/β-catenin and TGF-β, and EMT transcription factors, such as zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2. In addition, several microRNAs (miRNAs), including members of the miR-34 and miR-200 families, are found to target mRNAs of EMT-transcription factors, for example ZEB1, ZEB2, or SNAIL. Downregulation of these miRNAs is associated with distant metastasis and advanced stage tumors. Furthermore, the role of EMT in circulating tumor cells (CTCs) is also discussed. Mesenchymal markers on the surface of EMT CTCs were found to be associated with metastasis and could serve as potential biomarkers for metastasis. Altogether, these studies indicate that EMT is orchestrated by a complicated network, involving regulators of different signaling pathways. Further studies are required to understand the mechanisms underlying EMT in CRC.
Highlights
Colorectal cancer (CRC) remains the second leading cause of cancer death in the United States.More than 50% of CRC patients will develop liver metastases during their lifespan [1]
[23] Prospero Homeobox 1 (PROX1) [24], Forkhead Box Protein C2 (FOXC2) [25], Forkhead Box Q1 (FOXQ1) [26], FOXC1 [27], and Forkhead Box M1 (FOXM1) [28] are associated with invasiveness, metastasis, and poor prognosis of CRC
The loss of SMAD4 leads to aberrant activation of STAT3, which may directly contribute to the Epithelial to mesenchymal transition (EMT) process and zinc finger E-box binding homeobox 1 (ZEB1) expression in CRC progression
Summary
Colorectal cancer (CRC) remains the second leading cause of cancer death in the United States. Understanding the molecular mechanisms underlying these transitions, especially how colorectal cancer cells acquire invasive and metastatic properties, is important for the development of optimized strategies to treat CRC. Cancers 2017, 9, 171 evidence for the vital role that EMT plays in cancer progression and metastasis in many types of malignancies including CRC [8]. We will describe current knowledge about the mechanisms and regulators of EMT in CRC These regulators are aberrantly expressed in human CRC and their expression correlates with induction of EMT and cancer metastasis. We will discuss the importance of studying the role of EMT in metastasis, and how EMT can be considered as an applicable target for therapeutic strategies, especially for patients with CRC metastasis
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