Published online Aug 13, 2018. doi: 10.5306/wjco.v9.i4.60
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
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.