Endothelin-converting enzyme-1 in cancer aggressiveness
Author
dc.contributor.author
Tapia, Julio C.
Author
dc.contributor.author
Niechi, Ignacio
Admission date
dc.date.accessioned
2019-10-22T03:10:07Z
Available date
dc.date.available
2019-10-22T03:10:07Z
Publication date
dc.date.issued
2019
Cita de ítem
dc.identifier.citation
Cancer Letters, Volumen 452,
Identifier
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18727980
Identifier
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03043835
Identifier
dc.identifier.other
10.1016/j.canlet.2019.03.033
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/171868
Abstract
dc.description.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, ET A R, 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-1c 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.