TRAF6 regulates melanoma invasion and metastasis through ubiquitination of Basigin
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Zhongling Luo1, Xu Zhang1, Weiqi Zeng1, Juan Su1, Keda Yang2, Lixia Lu1, Chuan Bian Lim3, Wen Tang4, Lisha Wu5, Shuang Zhao1, Xuekun Jia1, Cong Peng1, Xiang Chen1
1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
2Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China
3Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
4Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China
5Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, Hunan, China
Cong Peng, e-mail: [email protected]
Xiang Chen, e-mail: [email protected]
Keywords: TRAF6, melanoma, invasion and metastasis, Basigin, ubiquitination
Received: September 07, 2015 Accepted: January 02, 2016 Published: January 12, 2016
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.
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