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World J Stem Cells. Aug 26, 2017; 9(8): 118-126
Published online Aug 26, 2017. doi: 10.4252/wjsc.v9.i8.118
Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance
Minal Garg
Minal Garg, Department of Biochemistry, University of Lucknow, Lucknow 226007, India
Author contributions: Garg M contributed to this paper.
Conflict-of-interest statement: Garg M declares no conflict-of-interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Minal Garg, Assistant Professor, Department of Biochemistry, University of Lucknow, University Road, Lucknow 226007, India. garg_minal@lkouniv.ac.in
Telephone: +91-93-35820857
Received: January 24, 2017
Peer-review started: February 2, 2017
First decision: March 28, 2017
Revised: May 22, 2017
Accepted: June 19, 2017
Article in press: June 20, 2017
Published online: August 26, 2017
Processing time: 211 Days and 10.7 Hours
Abstract

Epithelial-mesenchymal transition (EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells (CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surface markers and allow aberrant differentiation of progenies. It facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance. Based on the current information, present review discusses and summarizes the recent advancements on the molecular mechanisms that derive epithelial plasticity and its major role in generating a subset of tumor cells with stemness properties and pathophysiological spread of tumor. This paper further highlights the critical need to examine the regulation of EMT and CSC pathways in identifying the novel probable therapeutic targets. These improved therapeutic strategies based on the co-administration of inhibitors of EMT, CSCs as well as differentiated tumor cells may provide improved anti-neoplastic response with no tumor relapse.

Keywords: Epithelial-mesenchymal transition; Anticancer therapies; Cancer stem cells; Molecular pathogenesis; Tumor relapse

Core tip: Frequently observed reason for the failure in the treatment of malignant carcinomas is the biological programming of epithelial cells called epithelial-mesenchymal transition (EMT). It confers cancer cells, an ability to lose epithelial traits; gain mesenchymal traits; acquire stem-like properties; disseminate and colonize to distant organ sites and show elevated resistance to cancer therapies. Partial elimination of cancer stem cells and their propagation into secondary tumors post-treatment are the limitations associated with currently available standard of care including radio/chemotherapies, surgical resection or combination of these. Differentiation-based therapeutic strategies utilize the variable and regulatory powers of EMT program, lead to successful eradication of stem-like population of cancer cells by reverting the EMT phenotype and may hold great promise in improving the clinical outcomes.