Clinical significance of epithelial‐mesenchymal transition

Abstract

The concept of epithelial‐mesenchymal transition (EMT), a process where cells change their epithelial towards a mesenchymal phenotype, has gained overwhelming attention especially in the cancer research community. Thousands of scientific reports investigated changes in gene, mRNA and protein expression compatible with EMT and their possible correlation with tumor invasion, metastatic spread or patient prognosis; however, up to now, a proof of clinical significance of the concept is still missing. This review, with a main focus on the role of EMT in tumors, will summarize the basic molecular events underlying EMT including the signaling pathways capable of its induction as well as changes in EMT‐associated protein expression and will very briefly touch the role of microRNAs in EMT. We then outline protein markers that are used most frequently for the assessment of EMT in research and diagnostic evaluation of tumor specimens and depict the link between EMT, a cancer stem cell (CSC) phenotype and resistance to conventional antineoplastic therapies. Furthermore, we evaluate a possible correlation between EMT marker expression and patient prognosis as well as current therapeutic concepts targeting the EMT process to slow down or prevent metastatic spread of malignant tumors.

An important role of the hepcidin–ferroportin signaling in affecting tumor growth and metastasis

“…EMT is closely associated with metastasis, whereas inhibition of EMT could suppress metastasis [52,53]. Targeting the process of EMT appears to be a promising strategy to restrain cancer progression [54,55]. For instance, quite a few approaches have been developed to attenuate the TGF-β signaling, a key player of EMT [54,55].…”

Prospero homeobox 1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis

“…There is increasing evidence that EMT is a major contributor to tumor progression and metastasis and is associated with poor clinical outcomes of various cancers [29,30]. A study [31].…”

Intratumoral Heterogeneity: From Diversity Comes Resistance

“…For example, induction of epithelial-to-mesenchymal transition (EMT) converts immortalized breast epithelial cells into breast CSCs, rendering them more chemoresistant (18). EMT is recognized as a resistance mechanism to both kinase inhibitors and conventional chemotherapies (19,20). Additional signaling pathways have been implicated in conferring both stemness and resistance, including IL6, JAK/STAT, HGF, WNT, NOTCH, TGFB, PDGF, and others (16).…”