突变p53的获得性功能（GOF）是理解其癌基因特性的关键。我们前期研究发现突变蛋白p53S获得了调控Akt-mTOR通路蛋白Raptor/Rictor的功能，并可以调控Akt磷酸化水平。鉴于Akt-mTOR通路在肿瘤调控中的重要性，而突变p53对其调控的GOF鲜见报道，本项目将首先在细胞水平验证p53S对Akt-mTOR通路的调控作用，并人工干预肿瘤细胞内p53S或Akt-mTOR通路，再将肿瘤细胞进行体内移植形成肿瘤，验证p53S调控Akt-mTOR通路对肿瘤增殖和转移的作用。进一步在p53S/S小鼠自发肿瘤中，验证肿瘤组织内p53S表达、Akt-mTOR通路调控与肿瘤增殖的内在联系，本研究将初步阐明p53S调控Akt-mTOR通路对肿瘤细胞增殖和转移的影响，为临床预后及肿瘤个性化治疗提供科学依据。

The gain of function (GOF) of p53 mutant is very important for understanding its oncogenic features. Our previous studies showed that p53S mutant gain the function of regulating Akt-mTOR pathway associated Raptor/Rictor proteins and phosphorylation level of Akt. The Akt-mTOR pathway plays a key role in tumor, and the GOF of p53S mutant is rarely studied. We will first confirm the regulating effect of p53S mutant on Akt-mTOR pathway at the cellular level. Subsequently, we will transplant the tumor cells with expression alteration of p53S or Akt-mTOR pathway associated genes into mouse, and determine the effects of Akt-mTOR pathway regulated by p53S mutant on tumor growth and metastasis. In p53S/S mouse model with spontaneously developing tumor, we will examine the associations among p53S expression, Akt-mTOR pathway regulations and tumor growth. Our study will make a pilot study on the role of Akt-mTOR pathway regulated by p53S mutant on tumor cell growth and metastasis, and provide more scientific evidence for cancer patient prognosis prediction and personalized treatment design.