Survivin deficient Hepatocellular carcinoma and non-cancerous tissue of mice

Hepatocellular carcinoma (HCC) is a deadly cancer lacking efficacious therapies. Latest studies show that cellular senescence and inflammation play key roles in HCC development, likely reflecting its etiological nature of chronic infection. A better understanding of these intertwined processes would facilitate development of therapies for malignant HCCs. Here, we show that malignant HCCs are drastically reduced after deletion of Survivin, an inhibitor of apoptosis protein. Survivin deficiency induces mitosis defect-caused metabolism reprogram and senescence in HCC cells. Survivin additionally protects both senescent and neighboring non-senescent cancer cells from cell death triggered by senescence-associated inflammatory factor TNFα. Importantly, combination of mitosis inhibitor and pro-apoptosis drug, but not alone, synergistically eliminates HCCs, recapitulating the therapeutic effect of genetic deletion of Survivin. By uncovering the role of Survivin in controlling the interaction of senescence and inflammation responses, our findings propose a strategy for HCC therapy by inducing senescence and boosting TNFα-mediated cell death. Three samples are Survivin deleted HCC, three samples are Survivin wild type HCC. Three samples are Survivin deleted non-cancerous tissue, three samples are Survivin wild type non-cancerous tissue.