The E3 ligase COP1 promotes ERα signaling and suppresses EMT in breast cancer

[en] 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.

Disciplines :

Biochemistry, biophysics & molecular biology
Oncology

Author, co-author :

Tang, Seng Chuan

Lion, Quentin ; Université de Liège - ULiège > GIGA Stem Cells - Medical Chemistry

Peulen, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie dans le domaine des sc. médicales et biomédicales

Chariot, Philippe

Lavergne, Arnaud ; Université de Liège - ULiège > GIGA Platform Genomics

Mayer, Alice ; Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics

Allepuz Fuster, Paula

Close, Pierre ; Université de Liège - ULiège > GIGA Stem Cells - Cancer Signaling

Klein, Sebastian

Florin, Alexandra

More authors (4 more)

Language :

English

Title :

The E3 ligase COP1 promotes ERα signaling and suppresses EMT in breast cancer

Publication date :

29 January 2022

Journal title :

Oncogene

ISSN :

0950-9232

eISSN :

1476-5594

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Pages :

173-190

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 11 February 2022

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