An increasing number of studies highlight the role of mutant p53 proteins in cancer cell growth and in the worsening of cancer patients' clinical outcome. Autophagy has been widely recognized as a main biological event involved in both the regulation of cancer cell proliferation and in the response of several anticancer drugs. A thorough analysis of scientific literature underlines the reciprocal interplay between mutant p53 proteins and autophagy regulation. In this review, we analytically summarize recent findings, which indicate that gain-of-function (GOF) mutant p53 proteins counteract the autophagic machinery by various molecular mechanisms including the regulation of AMPK and Akt/mTOR pathways, autophagy-related genes (ATGs), HIF-1α target genes, and the mitochondrial citrate carrier CIC. Moreover, we report that mutant p53 protein stability is affected by lysosome-mediated degradation through macroautophagy or chaperone-mediated autophagy, suggesting the use of autophagy stimulators to counteract mutant p53 oncogenic activity. Finally, we discuss the functional role of the interplay between mutant p53 proteins and autophagy in cancer progression, a fundamental knowledge to design more effective therapies against cancers bearing mutant TP53 gene.

中文翻译：

---

突变型p53蛋白与癌细胞自噬之间的分子相互作用。

越来越多的研究突显了突变型p53蛋白在癌细胞生长和癌症患者临床预后恶化中的作用。自噬已被广泛认为是一种主要的生物学事件，涉及调节癌细胞的增殖以及参与多种抗癌药物的反应。对科学文献的透彻分析强调了突变体p53蛋白与自噬调节之间的相互影响。在这篇综述中，我们分析性地总结了最近的发现，这些发现表明功能获得（GOF）突变体p53蛋白通过多种分子机制（包括AMPK和Akt / mTOR通路，自噬相关基因（ATG）的调节）抵消了自噬机制。 ，HIF-1α靶基因和线粒体柠檬酸盐载体CIC。而且，我们报告突变体p53蛋白的稳定性受溶酶体介导的降解作用的影响，这些降解是通过巨噬自噬或伴侣介导的自噬而引起的，提示使用自噬刺激物来抵消突变体p53的致癌活性。最后，我们讨论了突变p53蛋白与自噬之间相互作用在癌症进展中的功能作用，这是设计针对携带突变TP53基因的癌症设计更有效疗法的基础知识。