Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition

Mutations in TP53 gene play a pivotal role in tumorigenesis and cancer development. Here, we report that gain-of-function mutant p53 proteins inhibit the autophagic pathway favoring antiapoptotic effects as well as proliferation of pancreas and breast cancer cells. We found that mutant p53 significantly counteracts the formation of autophagic vesicles and their fusion with lysosomes throughout the repression of some key autophagy-related proteins and enzymes as BECN1 (and P-BECN1), DRAM1, ATG12, SESN1/2 and P-AMPK with the concomitant stimulation of mTOR signaling.

Source: Molecular Oncology - April 11, 2016 Category: Cancer & Oncology Authors: Marco Cordani, Elisa Oppici, Ilaria Dando, Elena Butturini, Elisa Dalla Pozza, Mercedes Nadal-Serrano, Jordi Oliver, Pilar Roca, Sofia Mariotto, Barbara Cellini, Giovanni Blandino, Marta Palmieri, Silvia Di Agostino, Massimo Donadelli Source Type: research