Mutant p53 Regulates TNFSF10 in Cancer

Tumor suppressor protein p53 is an essential regulator of cell death.p53 activates genes that cause programmed cell death, or apoptosis, which stops damaged cells from dividing and suppresses cancer initiation and progression.About half of all human cancers carry p53 mutations, which affect the protein's normal function and can promote tumor growth.This study investigates the effects ofp53 mutation on the expression of TNFSF10, encoding the pro-apoptotic protein TRAIL.An analysis of transcriptomic data from the DepMap database showed that TNFSF10 is overexpressed in renal cell carcinoma (RCC) cell lines carrying mutant but not wild type p53.The function of TRAIL in promoting the survival of cancer cells was investigated through a literature review.Finally, analysis of drug sensitivity data from the Cancer Therapeutic Response Portal revealed that RCC cells with high expression of TRAIL show increased sensitivity to the bioactivated compound SNS-032.These data suggest that SNS-032 could be used as a treatment to selectively target mutant p53 RCC tumors characterized by high TRAIL expression. Research QuestionHow does mutation of p53 affect expression of apoptotic genes?Hypothesis Mutant p53 causes overexpression of genes that inhibit apoptosis to promote survival of RCC cells.