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Src-mediated phosphorylation, ubiquitination and degradation of Caveolin-1 promotes breast cancer cell stermness

Cited 5 time in Web of Science Cited 6 time in Scopus
Authors
Yoon, Hyo-Jin; Kim, Do-Hee; Kim, Su-Jung; Jang, Jeong-Hoon; Surh, Young-Joon
Issue Date
2019-05
Citation
Cancer Letters, Vol.449, pp.8-19
Keywords
Breast cancer stem cellCaveolin-1c-SrcPhosphorylationDestabilization
Abstract
Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and recurrence. Caveolin-1 (Cav-1) is a major protein of caveolae, which participates in various cellular functions, such as vesicle trafficking, cholesterol homeostasis, tumor progression, etc. In the present study, we investigated a role for Cav-1 in regulating the sternness of human breast cancer (MDA-MB-231) cells. Cav-1 expression was significantly lower in tumorspheres than in adherent cells. The silencing of Cav-1 enhanced sternness of MDA-MB-231 cells. Mechanistically, Cav-1 silencing was accompanied by enhanced expression of Bmi-1, which is a representative self-renewal regulator, and promoted epithelial-mesenchymal transition. In a CSC-like state, reduced Cav-1 depends on its destabilization through ubiquitin-proteasome degradation. We further found that Src-mediated phosphorylation of Cav-1 at the Tyr 14 residue is essential for its degradation. Taken together, these findings suggest that Cav-1 destabilization by Src may play a pivotal role in manifestation and maintenance of sternness in breast cancer cells.
ISSN
0304-3835
URI
https://hdl.handle.net/10371/172824
DOI
https://doi.org/10.1016/j.canlet.2019.01.021
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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