TRAF6 regulates melanoma invasion and metastasis through ubiquitination of Basigin.
TRAF6 regulates melanoma invasion and metastasis through ubiquitination of Basigin.
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TRAF6 通过 Basigin 泛素化调节黑色素瘤侵袭和转移。
DOI：
10.18632/oncotarget.6886
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发表时间：
2016-02-09
期刊：
影响因子：
--
通讯作者：
Chen X
中科院分区：
文献类型：
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作者：
Luo Z;Zhang X;Zeng W;Su J;Yang K;Lu L;Lim CB;Tang W;Wu L;Zhao S;Jia X;Peng C;Chen X
TRAF6在调节先天免疫和获得性免疫反应中起着至关重要的作用。尽管研究表明TRAF6具有致癌活性，但TRAF6在黑色素瘤中的作用尚不清楚。在这里，我们报告TRAF6在原发和转移性黑色素瘤肿瘤和黑色素瘤细胞系中过表达。用shRNA敲除TRAF6可显著抑制恶性表型，包括细胞增殖、非锚定细胞生长和体内、外转移。值得注意的是，我们证明了肿瘤细胞侵袭和转移的关键分子basigin(BSG)/CD147是TRAF6的新的相互作用伙伴。此外，通过shRNA耗尽TRAF6减少了BSG在质膜上的募集和K63连接的泛素化，从而削弱了BSG依赖的MMP9的诱导。综上所述，我们的发现表明TRAF6参与调节黑色素瘤的侵袭和转移，提示TRAF6可能是黑色素瘤治疗或化学预防的潜在靶点。
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.