Universität zu Köln

Tang, Seng Chuan ORCID: 0000-0002-8709-3531, Lion, Quentin, Peulen, Olivier ORCID: 0000-0002-6933-0134, Chariot, Philippe, Lavergne, Arnaud, Mayer, Alice ORCID: 0000-0002-6859-0612, Fuster, Paula Allepuz, Close, Pierre, Klein, Sebastian, Florin, Alexandra, Buettner, Reinhard, Nemazanyy, Ivan, Shostak, Kateryna and Chariot, Alain (2022). The E3 ligase COP1 promotes ER alpha signaling and suppresses EMT in breast cancer. Oncogene, 41 (2). S. 173 - 191. LONDON: SPRINGERNATURE. ISSN 1476-5594

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Abstract

ER alpha signaling drives proliferation, survival and cancer initiation in the mammary gland. Therefore, it is critical to elucidate mechanisms by which ER alpha 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 ER alpha expression and ER alpha-dependent gene transcription, at least through c-Jun degradation. COP1 and ER alpha 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 ER alpha signaling but also acts as a tumor suppressor candidate by preventing EMT, which reflects a dual role of COP1 in breast cancer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tang, Seng Chuan UNSPECIFIED orcid.org/0000-0002-8709-3531 UNSPECIFIED Lion, Quentin UNSPECIFIED UNSPECIFIED UNSPECIFIED Peulen, Olivier UNSPECIFIED orcid.org/0000-0002-6933-0134 UNSPECIFIED Chariot, Philippe UNSPECIFIED UNSPECIFIED UNSPECIFIED Lavergne, Arnaud UNSPECIFIED UNSPECIFIED UNSPECIFIED Mayer, Alice UNSPECIFIED orcid.org/0000-0002-6859-0612 UNSPECIFIED Fuster, Paula Allepuz UNSPECIFIED UNSPECIFIED UNSPECIFIED Close, Pierre UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Florin, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Nemazanyy, Ivan UNSPECIFIED UNSPECIFIED UNSPECIFIED Shostak, Kateryna UNSPECIFIED UNSPECIFIED UNSPECIFIED Chariot, Alain UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-588698
DOI:	10.1038/s41388-021-02038-3
Journal or Publication Title:	Oncogene
Volume:	41
Number:	2
Page Range:	S. 173 - 191
Date:	2022
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1476-5594
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ESTROGEN-RECEPTOR-ALPHA; REGULATES C-JUN; TUMOR-SUPPRESSOR; CELLS; EXPRESSION; TRANSCRIPTION; MECHANISMS; RESISTANCE; STABILITY; PHOSPHORYLATION Multiple languages Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58869