甲状腺乳头状癌(PTC)是最常见的内分泌恶性肿瘤，近期研究发现BRAFV600E作为预后不良的分子指标可调控细胞代谢过程。前期我们验证了BRAFV600E突变可以增强PTC细胞侵袭转移能力，并发现抗凋亡蛋白Mcl-1在一系列重要基因调控PTC的凋亡过程中发生变化，且影响糖代谢过程。国内外文献和已有数据提示Mcl-1可通过调控线粒体Drp1蛋白的表达从而改变线粒体分裂与融合的动态平衡，引起细胞代谢异常及侵袭转移能力改变。据此，我们提出BRAFV600E可能作为Mcl-1上游基因调控Mcl-1，进一步调控线粒体Drp1蛋白从而引起代谢异常并发挥生物学功能的假说。本课题拟探讨BRAFV600E在PTC中如何调控Mcl-1及其下游分子从而影响细胞代谢及侵袭转移的分子生物学机制，揭示BRAFV600E突变导致PTC预后不佳的新依据，为PTC治疗提供潜在靶点。

Papillary thyroid cancer (PTC) is the most common malignant endocrine tumor. As a biomarker for poor prognosis in PTC, recent research has discovered that BRAFV600E mutation can also regulate cell metabolism. Our previous work has confirmed that BRAFV600E mutation enhances PTC cell invasion and metastasis; and the level of Mcl-1 expression, an antiapoptotic protein, alters in the process of apoptosis induced by various of important genes, affecting glycolysis. Literature and our data both indicate that Mcl-1 balances the fission and fusion process of mitochondrial by targeting Drp1 protein, compromising cell metabolism and accordingly changing the potential of cell invasion and metastasis. Taken together, we speculate that BRAFV600E can function as an upstream gene of Mcl-1, which furthermore regulates Drp1 and changes cell metabolism, eventually promoting cell invasion and metastasis. This research aims to discuss the mechanism of how BRAFV600E regulates Mcl-1 and its downstream molecules, reveal the role of BRAFV600E in cell metabolism, invasion and metastasis, offer new evidence of BRAFV600E and PTC prognosis, and hopefully provide novel pharmaceutical targets for PTC.