Article (Scientific journals)
The E3 ligase COP1 promotes ERα signaling and suppresses EMT in breast cancer
Tang, Seng Chuan; Lion, Quentin; Peulen, Olivier et al.
2022In Oncogene, 41, p. 173-190
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Abstract :
[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
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
Büttner, Reinhard
Nemazanyy, Ivan
Shostak, Kateryna ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Chariot, Alain ;  Université de Liège - ULiège > GIGA Stem Cells - Medical Chemistry
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Title :
The E3 ligase COP1 promotes ERα signaling and suppresses EMT in breast cancer
Publication date :
29 January 2022
Journal title :
Publisher :
Nature Publishing Group, United Kingdom
Volume :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
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since 11 February 2022


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