HSF1 promotes the repopulation of post-senescent fatty hepatocellular carcinoma cell via modulating HSP90a/P53 complex stability.

HSP90 is a molecular chaperone extensively studied in the context of tumor development. Although burgeoning studies demonstrate that the activity and modification status of HSP90 are involved in maintaining and evolving the malignant phenotype of tumor, both during radiotherapy and chemotherapy-induced stress responses, the mechanistic intricacies tying HSP90-regulated cell senescence, serving as a pro-survival strategy, to tumor progression remain elusive. In this paper, we applied RNA-seq of Huh7 cells with HSP90 inhibitor 17-AAG treatment and its parent counterparts to determine the effect of HSP90 on HCC cell and its transcriptome differences. Our results showed that HSF1-HSP90a-P53 axis facilitated switching lipid metabolism from catabolism to anabolism during repopulation post-senescence, thereby maintaining HCC cell survival, which offers a promising therapeutic strategy for tumor prevention. Overall design: Cells were sorted as three groups based on 17-AAg treatment, including 17-AAG treatment group and untreated group (Control group). Three replicates were conducted to each group.