Endothelin-converting enzyme-1 in cancer aggressiveness

Tapia, J.C.; Niechi I.

Abstract

The endothelin-1 (ET-1) axis contributes to the pathophysiology of several cancers by promoting tumor development and progression. This peptide is activated from its precursor, big ET-1, by endothelin-converting enzyme-1 (ECE-1). Active ET-1 binds to its cognate G-coupled receptor, ETAR, which transduces the signal to the inside of the cell. ET-1 has a short half-life of about 90 s, so its biological effects are completely dependent on its enzymatic activation by ECE-1. Expression of ECE-1 is elevated in several tumors and cancer cell lines. There are four ECE-1 isoforms -ECE-1a, -1b, -1c, and -1d- which vary in terms of their subcellular localization and, in some cases, their effects on cancer-related properties such as proliferation and invasiveness. In this article, we review findings on the role of ECE-1, particularly isoform ECE-1c, in oncogenesis and malignant progression. We also review evidence regarding ECE-1 expression in several types of tumors and cancer cell lines. Recent findings from our laboratory and others allow us to speculate on the mechanism by which ECE-lc promotes cancer aggressiveness. Finally, we evaluate potential post-translational modifications of ECE-1c, highlighting phosphorylation by several kinases, as well as evidence pointing to a putative, non-canonical, ET-1-independent mechanism for promoting invasiveness. Taken together, current evidence suggests that ECE-1c contributes to cancer aggressiveness and plays a putative role as a key regulator of cancer progression. Therefore, we propose that this protein is a promising target for prognostic and therapeutic purposes.

Más información

Título según WOS: Endothelin-converting enzyme-1 in cancer aggressiveness
Título según SCOPUS: Endothelin-converting enzyme-1 in cancer aggressiveness
Título de la Revista: CANCER LETTERS
Volumen: 452
Editorial: Sciencedirect
Fecha de publicación: 2019
Página de inicio: 152
Página final: 157
Idioma: English
DOI:

10.1016/j.canlet.2019.03.033

Notas: ISI, SCOPUS