癌基因PIK3CA在乳腺癌中发生高频激活性突变，其编码蛋白PI3Kα持续活化能促进乳腺癌的发生发展，但其促癌转化机制尚不明确。本项目前期研究发现PI3Kα持续活化能诱导乳腺上皮细胞发生衰老并分泌衰老相关促癌因子。与经典癌基因诱导细胞衰老介导机制不同，项目前期研究发现CD10蛋白的高表达和N-糖基化修饰可能介导了PI3Kα活化诱导的细胞衰老。本项目拟基于癌蛋白PI3Kα活化诱导细胞衰老现象，利用生物信息学、分子生物学和细胞生物学等技术，挖掘PI3Kα调控CD10 mRNA表达的转录因子，分析CD10蛋白N-糖基化修饰后的生物学功能，解析CD10蛋白介导细胞衰老的机理，从而揭示PI3Kα介导细胞衰老的分子机制，为探明PI3Kα活化促癌机制、全面了解PI3Kα的生物学功能、靶向PI3Kα治疗乳腺癌提供依据。

The oncogenic PIK3CA is frequently mutated in breast cancer cases, and the consitutive activation of PI3Kα, which is encoded by PIK3CA, could promote the occurrence and development of breast cancer, but the mechanisms underlying the process are still needed to be elucidated. We found that activation of PI3Kα could induced cellular senescence in human mammary epithelial cells with pro-tumorigenic secretome. Unlike to the classic mechanisms of oncogene-induced senescence, PI3Kα-induced senescence is mediated by the expression and N-glycosylation of CD10. By using bioinformatics technology, molecular and cell biology experiments, this study aims to ascertain the regulation of CD10 mRNA expression by transcription factors, analysis the role of N-glycosylated CD10 in cellular senescence, clarity the detailed mechanisms of PI3Kα activation to the induction of cellular senescence and provide a basis for targeting PI3Kα to treat breast cancer.