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Safa. J Cancer Metastasis Treat 2020;6:36 Journal of Cancer
DOI: 10.20517/2394-4722.2020.55 Metastasis and Treatment

Review Open Access

Epithelial-mesenchymal transition: a hallmark in
pancreatic cancer stem cell migration, metastasis

formation, and drug resistance

Ahmad R. Safa

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Correspondence to: Dr. Ahmad R. Safa, Department of Pharmacology and Toxicology, Indiana University School of Medicine,
635 Barnhill Dr. MS A416, Indianapolis, IN 46202, USA. E-mail: asafa@iupui.edu
How to cite this article: Safa AR. Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis
formation, and drug resistance. J Cancer Metastasis Treat 2020;6:36. http://dx.doi.org/10.20517/2394-4722.2020.55
Received: 1 Jun 2020 First Decision: 24 Jul 2020 Revised: 18 Aug 2020 Accepted: 9 Sep 2020 Published: 27 Sep 2020

Academic Editor: Godefridus J. Peters Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic
ductal adenocarcinoma (PDAC). Tumor dissemination is associated with the activation of an epithelial-to-
mesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell-to-
cell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These
MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger the phenotypic
transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during
cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem
limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs)
or cancer-initiating cells in pancreatic tumors. PCSCs may represent sub-populations of tumor cells resistant to
therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the
cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence
of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers
of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen as well as the drug
transporter ABCG2 grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell
dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from
cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights
a linkage between CSC and EMT. In this review, The current understanding of the PCSCs, signaling pathways
regulating these cells, PDAC heterogeneity, EMT mechanism, and links between EMT and metastasis in PCSCs

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
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