Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer

Abstract

Epithelial-to-mesenchymal transition (EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer (CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical (IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapy- or radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMT-angiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.

Tumor Budding and Prognosis in Gastric Adenocarcinoma

“…Tumor buds have been shown to arise from parts of tumor expressing markers that are associated with epithelial-to-mesenchymal transition (EMT). 13 EMT has been shown to increase invasive and metastatic capabilities of cancer cells, 14 which might explain why patients with high tumor budding have worse outcomes than those who with low tumor budding. Several potential treatments that target EMT in different cancer types are being developed, 15 and could benefit gastric cancer patients with high tumor budding.…”

Role of Wnt/β-Catenin Signaling in the Chemoresistance Modulation of Colorectal Cancer

“…β-Catenin and Ecadherin form a complex in the area of cell-cell junction, providing the basis for cell-cell association [67]. Previous studies have shown that ectopic expression of Snail and Ecadherin causes EMT in colorectal cancer [68][69][70]. In CRC, loss of E-cadherin is concomitant with the deregulation of the Wnt/β-catenin signaling pathway and has been characterized as a trait of EMT cells [71].…”

Stromal Expression of Vimentin Predicts the Clinical Outcome of Stage II Colorectal Cancer for High-Risk Patients

“…Cancer cells undergoing EMT may acquire enhanced proliferation, invasion, and cell migration abilities, and malignant neoplastic cells may acquire resistance to conventional chemoradiotherapy [5]. In CRC, EMT has been shown to stimulate tumor angiogenesis and cancer stem cell traits, which indicates that targeting EMT could be a promising therapeutic strategy for patients with CRC [5].…”