title: Molecular interplay between mutant p53 proteins and autophagy in cancer cells.
abstract: 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.
authors.affiliation: Department of Neuroscience, Biomedicine and Movement, Biochemistry Section, University of Verona, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cordani
authors.affiliation: Department of Neuroscience, Biomedicine and Movement, Biochemistry Section, University of Verona, Verona, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Butera
authors.affiliation: Department of Neuroscience, Biomedicine and Movement, Biochemistry Section, University of Verona, Verona, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Pacchiana
authors.affiliation: Department of Neuroscience, Biomedicine and Movement, Biochemistry Section, University of Verona, Verona, Italy. Electronic address: massimo.donadelli@univr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Donadelli
mesh_terms: D001343:Autophagy / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; D016159:Tumor Suppressor Protein p53
keywords: Autophagy; Cancer; Mutant p53