Intrinsic and Extrinsic Modulators of the Epithelial to Mesenchymal Transition: Driving the Fate of Tumor Microenvironment

Edoardo D'Angelo; Rafael Soares Lindoso; Francesca Sensi; Salvatore Pucciarelli; Benedetta Bussolati; Marco Agostini; Federica Collino

doi:10.3389/fonc.2020.01122

Intrinsic and Extrinsic Modulators of the Epithelial to Mesenchymal Transition: Driving the Fate of Tumor Microenvironment

Front Oncol. 2020 Jul 24:10:1122. doi: 10.3389/fonc.2020.01122. eCollection 2020.

Authors

Edoardo D'Angelo^{1

2

3}, Rafael Soares Lindoso^{4

5

6}, Francesca Sensi^{3

7}, Salvatore Pucciarelli¹, Benedetta Bussolati⁸, Marco Agostini^{1

2

3}, Federica Collino^{4

9

10}

Affiliations

¹ First Surgical Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy.
² LIFELAB Program, Consorzio per la Ricerca Sanitaria-CORIS, Veneto Region, Padua, Italy.
³ Institute of Pediatric Research, Fondazione Citta della Speranza, Padua, Italy.
⁴ Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁶ Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
⁷ Department of Molecular Sciences and Nanosystems, Cà Foscari University of Venice, Venice, Italy.
⁸ Department of Medical Sciences, Molecular Biotechnology Center, University of Torino, Turin, Italy.
⁹ Department of Biomedical Sciences, University of Padova, Padua, Italy.
¹⁰ Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione Ca' Granda, IRCCS Policlinico di Milano, Milan, Italy.

Abstract

The epithelial to mesenchymal transition (EMT) is an evolutionarily conserved process. In cancer, EMT can activate biochemical changes in tumor cells that enable the destruction of the cellular polarity, leading to the acquisition of invasive capabilities. EMT regulation can be triggered by intrinsic and extrinsic signaling, allowing the tumor to adapt to the microenvironment demand in the different stages of tumor progression. In concomitance, tumor cells undergoing EMT actively interact with the surrounding tumor microenvironment (TME) constituted by cell components and extracellular matrix as well as cell secretome elements. As a result, the TME is in turn modulated by the EMT process toward an aggressive behavior. The current review presents the intrinsic and extrinsic modulators of EMT and their relationship with the TME, focusing on the non-cell-derived components, such as secreted metabolites, extracellular matrix, as well as extracellular vesicles. Moreover, we explore how these modulators can be suitable targets for anticancer therapy and personalized medicine.

Keywords: epithelial to mesenchymal transition; extracellular matrix; extracellular vesicles; personalized medicine; tumor microenvironment.

Publication types

Review