ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression
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 u...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383520305451 |
| _version_ | 1818968417909080064 |
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| author | Meng Yuan Xiaobing Chen Yitang Sun Li Jiang Zhongni Xia Kaixiong Ye Hong Jiang Bo Yang Meidan Ying Ji Cao Qiaojun He |
| author_facet | Meng Yuan Xiaobing Chen Yitang Sun Li Jiang Zhongni Xia Kaixiong Ye Hong Jiang Bo Yang Meidan Ying Ji Cao Qiaojun He |
| author_sort | Meng Yuan |
| collection | DOAJ |
| description | 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 in vitro and in vivo. Of interest, CLDN3 undergoes S-palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S-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 S-palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S-palmitoylation might be a potential strategy for ovarian cancer therapy. |
| first_indexed | 2024-12-20T14:04:22Z |
| format | Article |
| id | doaj.art-ca339e61354840a79421abd6901a67c9 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-20T14:04:22Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-ca339e61354840a79421abd6901a67c92022-12-21T19:38:18ZengElsevierActa Pharmaceutica Sinica B2211-38352020-08-0110814261439ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progressionMeng Yuan0Xiaobing Chen1Yitang Sun2Li Jiang3Zhongni Xia4Kaixiong Ye5Hong Jiang6Bo Yang7Meidan Ying8Ji Cao9Qiaojun He10Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Genetics, University of Georgia, Athens, GA 30602, USAZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaTongde Hospital of Zhejiang Province, Hangzhou 310012, ChinaDepartment of Genetics, University of Georgia, Athens, GA 30602, USAInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 100098, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Corresponding authors.Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Corresponding authors.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 in vitro and in vivo. Of interest, CLDN3 undergoes S-palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S-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 S-palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S-palmitoylation might be a potential strategy for ovarian cancer therapy.http://www.sciencedirect.com/science/article/pii/S2211383520305451Claudin-3ZDHHC12S-PalmitoylationOvarian cancerCancer progressionMembrane localization |
| spellingShingle | Meng Yuan Xiaobing Chen Yitang Sun Li Jiang Zhongni Xia Kaixiong Ye Hong Jiang Bo Yang Meidan Ying Ji Cao Qiaojun He ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression Acta Pharmaceutica Sinica B Claudin-3 ZDHHC12 S-Palmitoylation Ovarian cancer Cancer progression Membrane localization |
| title | ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression |
| title_full | ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression |
| title_fullStr | ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression |
| title_full_unstemmed | ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression |
| title_short | ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression |
| title_sort | zdhhc12 mediated claudin 3 s palmitoylation determines ovarian cancer progression |
| topic | Claudin-3 ZDHHC12 S-Palmitoylation Ovarian cancer Cancer progression Membrane localization |
| url | http://www.sciencedirect.com/science/article/pii/S2211383520305451 |
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