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Background   TP53  gene mutations occur in more than 50% of human cancers and the vast majority of these mutations in human cancers are missense mutations, which broadly occur in DNA binding domain (DBD) (Amino acids 102–292) and mainly reside in six “hotspot” residues.  TP53  G245C and R273H point mutations are two of the most frequent mutations in tumors and have been verified in several different cancers. In the previous study of the whole genome sequencing (WGS), we found some mutations of  TP53  DBD in esophageal squamous cell carcinoma (ESCC) clinical samples. We focused on two high-frequent mutations  TP53  p.G245C and  TP53  p.R273H and investigated their oncogenic roles in ESCC cell lines, p53-defective cell lines H1299 and HCT116 p53−/−.    Results  MTS and colony formation assays showed that mutant  TP53  G245C and R273H increased cell vitality and proliferation. Flow cytometry results revealed inhibition of ultraviolet radiation (UV)- and ionizing radiation (IR)- induced apoptosis and disruption of  TP53 -mediated cell cycle arrest after UV, IR and Nocodazole treatment. Transwell assays indicated that mutant  TP53  G245C and R273H enhanced cell migration and invasion abilities. Moreover, western blot revealed that they were able to suppress the expression of  TP53  downstream genes in the process of apoptosis and cell cycle arrest induced by UV, which suggests that these two mutations can influence apoptosis and growth arrest might be due, at least in part, to down-regulate the expression of P21, GADD45α and PARP.    Conclusions  These results indicate that mutant  TP53  G245C and R273H can lead to more aggressive phenotypes and enhance cancer cell malignancy, which further uncover  TP53  function in carcinogenesis and might be useful in clinical diagnosis and therapy of  TP53  mutant cancers.    Electronic supplementary material  The online version of this article (10.1186/s12860-018-0167-y) contains supplementary material, which is available to authorized users.

Mutant TP53 G245C and R273H promote cellular malignancy in esophageal squamous cell carcinoma