肾透明细胞癌的转移性强且死亡率高，然而其转移机制尚不清楚。自噬是细胞清除损伤细胞器和维持能量代谢平衡的主要方式，具有促进肿瘤转移的重要作用。我们前期发现FOXA2在肾透明细胞癌中的表达与术后转移密切相关，敲低FOXA2抑制肿瘤细胞自噬和转移；转录组测序发现FOXA2可调节AMPK复合体α亚基PRKAA2的转录表达，对自噬激活具有关键调节作用。我们推测：FOXA2可能通过转录调节PRKAA2激活自噬进而促进肾透明细胞癌浸润转移。本项目拟：①通过临床标本检测FOXA2与PRKAA2的表达相关性，并分析二者表达与转移预后的关系；②深入探究FOXA2转录调控PRKAA2激活自噬的具体机制；③探究PRKAA2及自噬对FOXA2促肾透明细胞癌转移的调控作用；④构建转移模型，检测干预FOXA2和自噬对肾透明细胞癌转移的影响。以此解析FOXA2促肾透明细胞癌转移的具体机制，为精准靶向治疗肾癌提供新思路。

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and has the highest propensity to metastasis and mortality, however, the mechanisms of ccRCC metastasis is still unclear. Autophagy plays an important role in promoting tumor cell metastasis by clearing damaged organelle, recycling metabolites and maintaining energy metabolism balance. Our latest studies showed that FOXA2 was highly expressed in ccRCC and its expression level was correlated with metastasis and poor prognosis. Knockdown of FOXA2 could inhibit autophagy and metastasis of ccRCC cells. RNA-seq results showed that FOXA2 could upregulate the expression of PRKAA2, an alpha subunit of AMPK complex and playing essential roles in activating autophagy flux. So we assumed that FOXA2 may promote ccRCC metastasis by transcriptional regulating PRKAA2 and inducing autophagy. Firstly this project will analyze co-expression of FOXA2 and PRKAA2 in ccRCC specimens and correlation of them with metastasis. Secondly we will focus on the mechanism of FOXA2 transcriptionally regulating PRKAA2 and activating autophagy. Thirdly we will investigate the effects of PRKAA2 and autophagy on metastasis of ccRCC. Finally we will establish metastatic models of ccRCC and evaluate the influence of FOXA2 and autophagy interference on tumor metastasis. This study will clarify the mechanism of FOXA2 promoting ccRCC metastasis and provide new theoretical basis for precision targeting therapy on ccRCC.