Melanoma is a very malignant disease and there are still no effective treatments.,CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth.,However, the function of CD147 and GLUT-1 in melanoma have not been completely understood.,Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue.,In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells.,Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199.,Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells.,In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT.,Our results could help validate CD147 as a new therapeutic target for treating melanoma.
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.