TRAF6信号轴通过调控黑素瘤分泌FGF19诱导肿瘤相关成纤维细胞活化进而促进黑素瘤侵袭转移机制研究

肿瘤微环境驻留的肿瘤相关成纤维细胞(CAFs)在促进黑素瘤进展中有着重要的作用，CAFs与肿瘤细胞之间存在着“cross-talk”，CAFs可与肿瘤细胞共同发展并获得肿瘤表型，使得它们可以在复杂的肿瘤微环境（TME）中存活并促进肿瘤的侵袭转移。但关于CAFs与黑素瘤之间存在的“cross-talk”如何影响黑素瘤侵袭转移相关研究相对较少，作用的具体分子机制仍未阐明。我们通过转录组测序分析发现肿瘤坏死因子受体相关因子6（TRAF6）信号可调控黑素瘤分泌成纤维细胞生长因子19(FGF19)，并进一步调控成纤维细胞向CAFs转变。因此我们假设：TRAF6信号轴通过调控黑素瘤分泌FGF19诱导CAFs活化，进而促进黑素瘤的侵袭转移。为此本项目拟通过细胞及动物实验结合临床标本分析证明该假说，项目的实施有望阐明TRAF6信号轴调控黑素瘤微环境的新机制，为黑色素瘤的精准治疗提供新靶点。

The CAFs resident in the tumor microenvironment play an important role in promoting melanoma progression.There is a "cross-talk" between CAFs and tumor cells. CAFs can develop with tumor cells and acquire tumor phenotype, so that they can survive in complex TME and promote tumor invasion and metastasis. However, there are relatively few related studies on how the "cross-talk" between CAFs and melanoma affects the invasion and metastasis of melanoma, and the mechanism have not been fully elucidated. Through transcriptome sequencing analysis, we found that tumor necrosis factor receptor-associated factor 6 (TRAF6) can regulate melanoma- secreting fibroblast growth factor 19 (FGF19), which lead to the transformation of fibroblasts into CAFs. Therefore, we hypothesize that the TRAF6 signal axis promotes the secretion of FGF19 by melanoma and causes activation of CAFs, thereby promoting the invasion and metastasis of melanoma. This hypothesis will be tested by in vitro and in vivo experiments combined with analysis of clinical samples. The implementation of the project is expected to elucidate the new mechanism of TRAF6 signal regulation of melanoma microenvironment, and provide a new target for the precise treatment of melanoma.