TRAF6 regulates melanoma invasion and metastasis through ubiquitination of Basigin

Oncotarget
Zhongling LuoXiang Chen

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.

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Citations

Mar 27, 2018·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Yancan LiangBin Zhang
Dec 2, 2017·Journal of Cellular and Molecular Medicine·Lei ChenZhi-Jun Sun
Feb 14, 2018·International Journal of Molecular Medicine·Qingbing MengMinqian Zheng
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Jun 14, 2019·Frontiers in Endocrinology·Shehua QianXianquan Zhan
Sep 10, 2020·Cancer Cell International·Jiaoduan LiCong Peng
Sep 7, 2020·World Journal of Surgical Oncology·Wan-Ping GuoWei Ma
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Nov 13, 2019·The International Journal of Biochemistry & Cell Biology·Farjana Yeasmin KhusbuHan-Chun Chen
Jan 13, 2021·International Journal of Molecular Sciences·Justyna MazurkiewiczDorota Nowak
Mar 25, 2019·Life Sciences·Dhivya KumarKrishna Kumar Subramanian

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Methods Mentioned

BETA
ubiquitination
xenograft
xenografts
immunoprecipitation
glycosylation
transfection
Protein Assay
PCR

Software Mentioned

Prism
Image J

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