ZDHHC12-mediated claudin-3 -palmitoylation determines ovarian cancer progression.
10.1016/j.apsb.2020.03.008
- Author:
Meng YUAN
1
;
Xiaobing CHEN
1
;
Yitang SUN
2
;
Li JIANG
1
;
Zhongni XIA
3
;
Kaixiong YE
2
;
Hong JIANG
4
;
Bo YANG
1
;
Meidan YING
1
;
Ji CAO
1
;
Qiaojun HE
1
Author Information
1. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
2. Department of Genetics, University of Georgia, Athens, GA 30602, USA.
3. Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
4. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 100098, China.
- Publication Type:Journal Article
- Keywords:
Cancer progression;
Claudin-3;
Membrane localization;
Ovarian cancer;
S-Palmitoylation;
ZDHHC12
- From:
Acta Pharmaceutica Sinica B
2020;10(8):1426-1439
- CountryChina
- Language:English
-
Abstract:
The membrane protein claudin-3 (CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both and Of interest, CLDN3 undergoes -palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3 Moreover, the deprivation of -palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins. Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis Thus, our work reveals -palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 -palmitoylation might be a potential strategy for ovarian cancer therapy.
