Akt是一种丝氨酸/苏氨酸蛋白激酶，它的过度激活在肾癌发生发展中起重要作用。本研究前期实验发现，SAV1在肾癌中通过与Akt蛋白相互作用，负性调控Akt磷酸化，抑制肾癌细胞生长。目前调控SAV1和Akt相互作用的机制尚不清楚。SIK是一种高度保守的丝氨酸/苏氨酸蛋白激酶，在肿瘤增殖、凋亡等信号通路中起重要调控作用。有研究表明，在果蝇中Sik2、Sik3可以与Sav结合并使其磷酸化；SIK2、SIK3高表达是肿瘤预后不良因素，抑制SIK2表达可以下调 Akt磷酸化水平，抑制肿瘤生长。基于上述研究背景和前期实验基础，我们提出以下项目假说：SIK在肾癌中可能通过与SAV1结合并使其磷酸化从而参与SAV1对Akt磷酸化的负性调控。本研究在前期工作基础上，以阐明SIK参与SAV1负性调控Akt磷酸化的分子机制为目的，有望为肾癌的发生发展提供新的机制，为肾癌的治疗提供新的分子靶点。

Akt is a serine/threonine protein kinase, and its overactivation plays an important role in the development of renal cell carcinoma. Previous study found that SAV1 negatively regulates Akt phosphorylation and inhibits the growth of renal cell carcinoma by interacting with Akt protein. At present, the mechanism of regulating the interaction between SAV1 and Akt is not clear. SIK is a highly conserved serine/threonine protein kinase, which plays an important regulatory role in tumor proliferation, apoptosis and other signaling pathways. Research has shown that Sik2 and Sik3 can bind to Sav and phosphorylate it in Drosophila melanogaster. Besides, it has been reported that the high expression of SIK2 and SIK3 is a poor prognostic factor of cancer. Inhibiting SIK2 expression can down-regulate Akt phosphorylation and inhibit tumor growth. Based on previous experimental results, we propose the following hypothesis: SIK may be involved in SAV1 negative regulation of Akt phosphorylation by binding to and phosphorylating SAV1. On the basis of previous work, this study aims to elucidate the molecular mechanism of SIK involvement in SAV1 negative regulation of Akt phosphorylation, which is expected to provide a new mechanism for the occurrence and development of renal cell carcinoma and a new molecular target for the treatment of renal cell carcinoma.