Journal
ONCOTARGET
Volume 7, Issue 6, Pages 7179-7192Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6886
Keywords
TRAF6; melanoma; invasion and metastasis; Basigin; ubiquitination
Categories
Funding
- National Science Foundation for Distinguished Young Scholars [81225013]
- Fundamental Research of China
- National Natural Science Foundation [81572679]
- Natural Science Foundation of Hunan province [2015JJ2161]
- National Natural Science Youth Foundation [81201225, 81402263]
- key project of the National Science Foundation [81430075]
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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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