Tecalco-Cruz AC, Ramírez-Jarquín JO. Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer. World J Clin Oncol 2018; 9(4): 60-70 [PMID: 30148069 DOI: 10.5306/wjco.v9.i4.60]
Corresponding Author of This Article
Angeles C Tecalco-Cruz, PhD, Full Professor, Programa de Investigación de Cáncer de Mama (PICM), Departamento de Biología Moleculary Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México 04510, México. 12anget@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Aug 13, 2018; 9(4): 60-70 Published online Aug 13, 2018. doi: 10.5306/wjco.v9.i4.60
Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer
Angeles C Tecalco-Cruz, Josué O Ramírez-Jarquín
Angeles C Tecalco-Cruz, Programa de Investigación de Cáncer de Mama (PICM), Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México 04510, México
Josué O Ramírez-Jarquín, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México 04510, México
Author contributions: Tecalco-Cruz AC participated in the research, organization of this article and wrote the manuscript; Ramírez-Jarquín JO participated in the research, and improvement of this article and all figures of this article.
Supported bythe DGAPA-UNAM, Nos. PAPIIT-IA200916 and PAPIIT-IA201618.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Angeles C Tecalco-Cruz, PhD, Full Professor, Programa de Investigación de Cáncer de Mama (PICM), Departamento de Biología Moleculary Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México 04510, México. 12anget@gmail.com
Telephone: +52-55-56229208
Received: April 27, 2018 Peer-review started: April 27, 2018 First decision: June 15, 2018 Revised: June 22, 2018 Accepted: June 28, 2018 Article in press: June 29, 2018 Published online: August 13, 2018 Processing time: 108 Days and 6.9 Hours
Abstract
Estrogen receptor alpha (ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifications, interactions with coregulators, and formation of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.
Core tip: The inhibition of the estrogen receptor alpha polyubiquitination and degradation by several molecular mechanisms is related to the progression of breast cancer and resistance to endocrine therapy.
