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Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer

Angeles C Tecalco-Cruz1, Josué O Ramírez-Jarquín2

  • 1Programa 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. 12anget@gmail.com.

World Journal of Clinical Oncology
|August 28, 2018
PubMed

Insights

Inhibition of estrogen receptor alpha (ERα) polyubiquitination is linked to breast cancer progression and endocrine therapy resistance. Understanding these mechanisms is crucial for developing new cancer treatments.

Area of Science:

  • Molecular Biology
  • Oncology
  • Endocrinology

Background:

  • Estrogen receptor alpha (ERα) is a key factor in over 70% of breast cancers.
  • ERα's nuclear activity drives tumor development, while extranuclear activity correlates with endocrine therapy resistance.

Purpose of the Study:

  • To explore the role of ERα polyubiquitination in breast cancer progression.
  • To investigate mechanisms inhibiting ERα polyubiquitination and their impact on cancer signaling.

Main Methods:

  • Review of existing literature on ERα ubiquitination and its regulation.
  • Analysis of the relationship between ERα polyubiquitination, posttranslational modifications, and protein interactions.

Main Results:

  • ERα polyubiquitination is induced by estradiol and selective estrogen receptor degraders, leading to proteasomal degradation.
  • Inhibition of ERα polyubiquitination by various mechanisms increases ERα protein levels and dysregulates its signaling.
  • E3-ubiquitin ligases involved in ERα polyubiquitination can also act as coactivators.

Conclusions:

  • ERα polyubiquitination inhibition is a significant factor in breast cancer progression.
  • Dysregulated ERα signaling due to inhibited polyubiquitination contributes to endocrine therapy resistance.
Keywords:
Breast cancerEstrogen receptor alphaEstrogen receptor alpha polyubiquitination

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