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

被引:17
|
作者
Yoon, Hyo-Jin [1 ]
Kim, Do-Hee [1 ,2 ]
Kim, Su-Jung [1 ]
Jang, Jeong-Hoon [1 ]
Surh, Young-Joon [1 ,2 ,3 ]
机构
[1] Seoul Natl Univ, Coll Pharm, Tumor Microenvironm Global Core Res Ctr, Seoul 08826, South Korea
[2] Seoul Natl Univ, Coll Pharm, Dept Mol Med & Biopharmaceut Sci, Seoul 08826, South Korea
[3] Seoul Natl Univ, Canc Res Inst, Seoul 03080, South Korea
基金
新加坡国家研究基金会;
关键词
Breast cancer stem cell; Caveolin-1; c-Src; Phosphorylation; Destabilization; EPITHELIAL-MESENCHYMAL TRANSITIONS; STEM-CELLS; TYROSINE PHOSPHORYLATION; IN-VIVO; ACTIVATION; PLASTICITY; GROWTH; ASSOCIATION; ADHESION; ANOIKIS;
D O I
10.1016/j.canlet.2019.01.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:8 / 19
页数:12
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