The E3 ligase COP1 promotes ERα signaling and suppresses EMT in breast cancer.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
31
05
2021
accepted:
23
09
2021
revised:
14
09
2021
pubmed:
31
10
2021
medline:
17
2
2022
entrez:
30
10
2021
Statut:
ppublish
Résumé
ERα signaling drives proliferation, survival and cancer initiation in the mammary gland. Therefore, it is critical to elucidate mechanisms by which ERα expression is regulated. We show that the tumor suppressor E3 ligase COP1 promotes the degradative polyubiquitination of the microtubule-associated protein HPIP. As such, COP1 negatively regulates estrogen-dependent AKT activation in breast cancer cells. However, COP1 also induces ERα expression and ERα-dependent gene transcription, at least through c-Jun degradation. COP1 and ERα levels are positively correlated in clinical cases of breast cancer. COP1 also supports the metabolic reprogramming by estrogens, including glycolysis. On the other hand, COP1 suppresses EMT in breast cancer cells. COP1 deficiency also contributes to Tamoxifen resistance, at least through protective autophagy. Therefore, COP1 acts as an oncogenic E3 ligase by promoting ERα signaling but also acts as a tumor suppressor candidate by preventing EMT, which reflects a dual role of COP1 in breast cancer.
Identifiants
pubmed: 34716429
doi: 10.1038/s41388-021-02038-3
pii: 10.1038/s41388-021-02038-3
doi:
Substances chimiques
ESR1 protein, human
0
Estrogen Receptor alpha
0
COP1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
173-190Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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