title: TRAF6 regulates melanoma invasion and metastasis through ubiquitination of Basigin.
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.
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Keda
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Chuan Bian
authors.initials: CB
authors.lastname: Lim
authors.affiliation: Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tang
authors.affiliation: Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D051926:Basigin / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: C497886:BSG protein, human; D048029:TNF Receptor-Associated Factor 6; D025801:Ubiquitin; D051926:Basigin
keywords: Basigin; TRAF6; invasion and metastasis; melanoma; ubiquitination