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Nearly half of human cancers harbor p53 mutations, and mutant p53 (mutp53) promotes carcinogenesis, metastasis, tumor recurrence and chemoresistance. mutp53 is observed in 30% of breast carcinomas, including triple‐negative breast cancer (TNBC), and thus mutp53 is a promising target for treatment of TNBC. In this study, we investigated the effect of a phosphatidylinositide 3 kinase/mammalian target of rapamycin dual inhibitor, NVP‐BEZ235 (BEZ235), on two TNBC cell lines with mutp53: MDA‐MB‐231 and MDA‐MB‐468. Cell growth, migration and colony‐formation abilities were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide, scratch assay, transwell and soft agar assay, revealing that BEZ235 can inhibit the growth, migration and colony‐formation abilities of TNBC cells. In addition, BEZ235 caused degradation of mutp53 in these cells. We investigated the underlying mechanism by inhibiting proteasome function using MG132 and inhibiting autophagy using 3‐methyladenine and shRNAs. We observed that BEZ235 may induce autophagy through repression of the Akt/mammalian target of rapamycin signaling pathway. The observed interplay between mutp53 and autophagy in TNBC cells was examined further by knockdown of ATG5 and ATG7, revealing that degradation of mutp53 induced by BEZ235 may be independent of the ubiquitin–proteasome pathway and autophagy mediated by ATG5 and ATG7. Moreover, we found evidence of positive feedback between mutp53 and autophagy in TNBC cells. In conclusion, BEZ235 may exert antitumor effects against TNBC cells by targeting mutp53, and this may have implications for the development of future therapies., NVP‐BEZ235 is a phosphatidylinositide 3 kinase/mammalian target of rapamycin dual inhibitor, which exerts an antitumor effect against two triple‐negative breast cancer cell lines harboring mutant p53 protein: MDA‐MB‐231 and MDA‐MB‐468. BEZ235 induces autophagy in these cells, possibly through repression of the AKT/mammalian target of rapamycin pathway. Degradation of mutant p53 induced by BEZ235 is independent of the ubiquitin–proteasome pathway and autophagy. BEZ235 may be a potential therapeutic target for triple‐negative breast cancers with mutant p53.

Hepatocellular carcinoma (HCC) is a worldwide malignancy. To date, surgery is still the most effective treatment with curative potential, but only about 20% of patients with HCC are eligible for surgical intervention. Therefore exploring the pathogenesis of liver cancer, looking for molecules targeting therapy, is very important. Telomeres, the chromosome extremities, are protected by specific proteins, such as POT1, RAP1, TIN2, TRF1, TRF2,and TPP1. More and more findings have discovered that TPP1 plays an important role in the tumorigenesis. However, the mechanism of TPP1 in HCC remains unknown. The purpose of this study is to explore the role of TPP1 in HCC. Currently 42 cases of HCC patients were recruited in this study. First, the patients' tumor tissue, adjacent tissue and normal tissue were analyzed by Western blot. The results showed that TPP1 expression in patients' adjacent tissue and normal tissue was lower than that in tumor tissue, respectively (P Citation Format: Jiang Zou, Ru Sun, Jingruo Xia, Dan Xiao, Chang Liu, Hebin Liao, Lei Xu, Qiang Ma, Yan Cai, Jingdong Li, Xiaolan Guo. The role of telomere protective protein TPP1 in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 341.