转移性肾癌患者死亡率高，预后差，其治疗是临床的难点和热点问题。舒尼替尼（Sunitinib）等酪氨酸激酶抑制剂是转移性肾癌的一线治疗药物，但目前对Sunitinib耐受机制和调控通路的理解仍不透彻。申请者前期研究发现：在肾癌中EphA2高表达促进肾癌的转移和Sunitinib耐药，TCGA分析发现耐药相关基因YB1与EphA2呈正相关且在Sunitinib耐受细胞中表达上调，YB1正向调控EphA2的表达。据此提出YB1/EphA2信号通路是转移性肾癌病人对Sunitinib治疗耐受的关键信号通路。本项目拟分析肾癌临床标本中YB1和EphA2的表达及其相关性，在Sunitinib耐受肾癌细胞系及裸鼠原位瘤模型中，观察YB1/EphA2对转移性肾癌Sunitinib耐受的影响，并研究YB1/EphA2信号通路的调控机制，期望为转移性肾癌Sunitinib治疗耐受提供新的治疗策略和思路。

The patients with metastatic renal cancers have high mortality and poor prognosis. The treatment of metastatic renal cancers is the focus of attention and hot spots for clinicians. Sunitinib, a tyrosine kinase inhibitor, is the first-line drug for patients with metastatic renal cancers, but the current understanding on the mechanism of Sunitinib tolerance and regulatory pathways remains unclear. Previously applicants have found that high expression of EphA2 promoted metastasis and was related with Sunitinib tolerance in renal cancers. TCGA analysis showed that YB1 was positively correlated with EphA2 and up-regulated in Sunitinib-resistant cells. YB1 could up-regulate EphA2 expression in renal cancer cell lines. Accordingly, it is proposed that the YB1 / EphA2 signaling pathway may be a key signaling pathway for the tolerance of Sunitinib in patients with metastatic renal cancer. This project determines to analyze the expression of YB1 and EphA2 and their correlation in the clinical specimens of renal cancers. The Sunitinib-resistant renal cancer cell lines and nude mice in situ tumor model were selected for observing the effects of YB1 / EphA2 on the tolerance of Sunitinib in metastatic renal cancers. The regulatory mechanism of YB1 / EphA2 signaling pathway was also observed. This study may provide new strategies and ideas for the treatment of metastatic renal cancers.