TAZ Regulates Bladder Cancer Cell Proliferation and Apoptosis via p38 Activity

Abstract Background The progression of cancer is driven by the deregulation of various signaling pathways, especially Hippo and p38 MAPK pathway. TAZ, a downstream target of Hippo pathway, has been demonstrated to promote tumorigenesis in various cancers, but the functions of both Hippo and p38 signaling in bladder cancer cells are still unclear. Methods T24 and 5637 cells with knockdown of TAZ were constructed. EdU cell proliferation assay and western blot were used to illustrate the effects of TAZ on the proliferation and apoptosis of bladder cancer cells and the expression of p38 protein and phosphorylation. We overexpressed Flag-tagged TAZ in 293T cells. Western blot and RT-qPCR were used to further illustrate the effect of TAZ on the expression level of p38. The p38 inhibitor (PH-797804) combined with western blot and EDU cell proliferation assay were used to show whether TAZ affects the proliferation and apoptosis of bladder cancer cells by regulating the activity of p38.Results The shTAZ contained in T24 and 5637 cells significantly inhibited bladder cancer cells proliferation, in addition, the knockdown of TAZ-induced apoptosis of T24 and 5637 cells was found out. The loss of TAZ led to the upregulation of p38 protein as well as phosphorylation. The over-expression of Flag-TAZ had no obvious effect on p38 mRNA level, but p38 protein was reduced clearly in 293T cells. ShTAZ induced the upregulation of cleaved-caspase 3, which disappeared when treated with PH-797804, a p38 inhibitor, and the reduction to EdU positive cells induced by shTAZ was reversed by PH-797804 treatment, which suggested that p38 activity could mediate both cell proliferation and apoptosis regulated by TAZ knockdown. Conclusions In this study, it was demonstrated that TAZ could regulate the proliferation and apoptosis of bladder cancer cells by regulating the stability of p38 protein. Our finding uncovered the novel functional interaction between Hippo and p38 MAPK pathway. An in-depth understanding of this question may indicate a new direction of diagnosis or treatment for bladder cancer.