TRAF6 regulates melanoma invasion and metastasis through ubiquitination of Basigin
| Autor: | Shuang Zhao, Xiang Chen, Xu Zhang, Wen Tang, Lisha Wu, Zhongling Luo, Juan Su, Cong Peng, Keda Yang, Xuekun Jia, Weiqi Zeng, Chuan Bian Lim, Lixia Lu |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms Fluorescent Antibody Technique Apoptosis MMP9 Metastasis Immunoenzyme Techniques Small hairpin RNA Mice 0302 clinical medicine Ubiquitin Cell Movement Tumor Cells Cultured Mice Inbred BALB C biology Melanoma Oncology 030220 oncology & carcinogenesis Melanocytes TRAF6 Research Paper Blotting Western Mice Nude ubiquitination 03 medical and health sciences melanoma Cell Adhesion medicine Animals Humans Immunoprecipitation Neoplasm Invasiveness Cell Proliferation TNF Receptor-Associated Factor 6 Wound Healing Cell growth business.industry medicine.disease invasion and metastasis Xenograft Model Antitumor Assays 030104 developmental biology Basigin Immunology Cancer cell biology.protein Cancer research business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Zhongling Luo 1 , Xu Zhang 1 , Weiqi Zeng 1 , Juan Su 1 , Keda Yang 2 , Lixia Lu 1 , Chuan Bian Lim 3 , Wen Tang 4 , Lisha Wu 5 , Shuang Zhao 1 , Xuekun Jia 1 , Cong Peng 1 , Xiang Chen 1 1 Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China 2 Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China 3 Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA 4 Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China 5 Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, Hunan, China Correspondence to: Cong Peng, e-mail: pengchongpeng@hotmail.com Xiang Chen, e-mail: chenxiangck@126.com Keywords: TRAF6, melanoma, invasion and metastasis, Basigin, ubiquitination Received: September 07, 2015 Accepted: January 02, 2016 Published: January 12, 2016 ABSTRACT TRAF6 plays a crucial role in the regulation of the innate and adaptive immune responses. Although studies have shown that TRAF6 has oncogenic activity, the role of TRAF6 in melanoma is unclear. Here, we report that TRAF6 is overexpressed in primary as well as metastatic melanoma tumors and melanoma cell lines. Knockdown of TRAF6 with shRNA significantly suppressed malignant phenotypes including cell proliferation, anchorage-independent cell growth and metastasis in vitro and in vivo . Notably, we demonstrated that Basigin (BSG)/CD147, a critical molecule for cancer cell invasion and metastasis, is a novel interacting partner of TRAF6. Furthermore, depletion of TRAF6 by shRNA reduced the recruitment of BSG to the plasma membrane and K63-linked ubiquitination, in turn, which impaired BSG-dependent MMP9 induction. Taken together, our findings indicate that TRAF6 is involved in regulating melanoma invasion and metastasis, suggesting that TRAF6 may be a potential target for therapy or chemo-prevention in melanoma. |
| Databáze: | OpenAIRE |
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