U-box ubiquitin ligase PPIL2 suppresses breast cancer invasion and metastasis by altering cell morphology and promoting SNAI1 ubiquitination and degradation.
U-box ubiquitin ligase PPIL2 suppresses breast cancer invasion and metastasis by altering cell morphology and promoting SNAI1 ubiquitination and degradation.
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U-box泛素连接酶PPIL2通过改变细胞形态并促进SNAI1泛素化和降解来抑制乳腺癌侵袭和转移
DOI：
10.1038/s41419-017-0094-4
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发表时间：
2018-01-19
影响因子：
9
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Jia Z;Wang M;Li S;Li X;Bai XY;Xu Z;Yang Y;Li B;Li Y;Wu H
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear. Herein, we demonstrate that PPIL2 suppressed metastasis in a breast cancer model by altering cell morphology and suppressing the epithelial–mesenchymal transition (EMT) process. Moreover, elevated PPIL2 inhibited EMT and breast cancer invasion by interacting with the classical EMT transcription factor, SNAI1, to enhance its ubiquitin-dependent degradation. Furthermore, PPIL2 protein level and stability was upregulated after CsA treatment, indicating that PPIL2 might be involved in CsA-mediated repression of EMT in breast cancer. Analysis of tissue samples taken from breast cancer patients showed a significant correlation between the expression of PPIL2 and the degree of cancer invasion and metastasis. In summary, these results would shed light on a potential clinical use of CsA in breast cancer patients.
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影响因子：
254.7
作者：
DeSantis, Carol E.;Fedewa, Stacey A.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
4.3
作者：
Calhoun, Colonya C.;Lu, Ying-Chun;Chiu, Robert
通讯作者：
Chiu, Robert
影响因子：
254.7
作者：
DeSantis, Carol;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
9.7
作者：
Jin, Yue;Shenoy, Anitha K.;Doernberg, Samuel;Chen, Hao;Luo, Huacheng;Shen, Huangxuan;Lin, Tong;Tarrash, Miriam;Cai, Qingsong;Hu, Xin;Fiske, Ryan;Chen, Ting;Wu, Lizi;Mohammed, Kamal A.;Rottiers, Veerle;Lee, Siu Sylvia;Lu, Jianrong
通讯作者：
Lu, Jianrong
DOI：
10.1083/jcb.141.2.443
发表时间：
1998-04-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gindhart JG Jr;Desai CJ;Beushausen S;Zinn K;Goldstein LS
通讯作者：
Goldstein LS