结直肠癌是严重威胁国民健康的恶性肿瘤，寻找肿瘤相关基因阐明其生物学特征有重要意义。前期研究发现：OLA1在结直肠癌中表达升高，且与不良预后相关；OLA1敲除的肠癌细胞生长受抑，提示OLA1参与结直肠癌细胞的生长过程。机制探索发现OLA1敲低的肠癌细胞中p53蛋白表达上调，蛋白半衰期延长。结合文献报导：OLA1与HSP70直接结合；HSP70敲除后p53蛋白降解减少，由此假设: OLA1通过HSP70降解p53蛋白促进结直肠癌细胞生长。本研究拟构建OLA1差异表达的肠癌细胞和肠道OLA1特异性敲除的小鼠经体内外实验明确OLA1在结直肠癌细胞生长中的作用，并通过小分子抑制剂、基因敲降/过表达技术鉴定p53是OLA1影响结直肠癌细胞生长的关键分子，最后验证OLA1与HSP70的相互作用及其调控p53促进结直肠癌细胞生长的具体机制。该研究可丰富结直肠癌发生发展机制，为临床干预提供潜在靶点。

Colorectal cancer (CRC) is one of the most malignant tumors in China, which threatening the health of citizens. Illustrate the biological features of cancer cells by detecting cancer associated gene is good for the diagnosis and cure of cancer. The expression of OLA1 is heavily elevated in CRC than intestinal mucosa. Higher expression of OLA1 predicts poor survival. Besides, OLA1 knock out CRC cells represent growth retardation. These data indicated that OLA1 is a cancer associated gene in the process of colorectal cancer growth. To further investigation, we found p53 protein elevated in OLA1 knock out CRC cells, which ascribed to the prolonged degradation. Previous studies have proved that OLA1 interacts with HSP70, meanwhile, HSP70 promoted the degradation of p53. So, we hypothesize that OLA1 interacts with HSP70 to promote the growth of CRC by degrading p53.This proposal focuses on 3 parts: First, verify the role of OLA1 in the process of CRC growth by OLA1 overexpression or knock out CRC cells and OLA1 conditional knock out mice; Then, clarify p53 is central for OLA1 promoting CRC growth by gene knock down and small molecular inhibitor; Finally, explore the direct interactions between OLA1 and HSP70. The study will enrich the mechanism of CRC formation and development, and provide potential target for clinical treatment.