TAZ promotes cell growth and inhibits Celastrol-induced cell apoptosis.

Hippo pathway is a highly conservative signaling pathway related to the development of organisms, which has been demonstrated to be strongly linked to the tumorigenesis and tumor progression. As the major downstream effector of Hippo pathway, yes-associated protein (YAP), is a transcriptional activator of target genes that are involved in cell proliferation and survival. As an oncogene, YAP can promote cell growth and inhibit cell apoptosis. Another major downstream effector of Hippo pathway, transcriptional coactivators with PDZ-binding motif(TAZ), is nearly 60% homologous with YAP. Here, we assume that TAZ probably has the similar function to YAP. To test this issue, we established an inducible and a stable expression system of TAZ in T-Rex-293 and HEK293 cells, respectively. The results of cell growth curves, colony formation assay and tumor xenograft growth showed that overexpression of TAZ could promote cell growth in vitro and in vivo Meanwhile, we found that up-regulated expression of TAZ could partially restore Celastrol-induced cell apoptosis. Induced overexpression of TAZ could upregulate its target genens including ankyrin repeat domain containing protein(ANKRD), cysteine rich 61(CYR61) and connective tissue growth factor(CTGF), increase the expression of Bcl-2, decrease the expression of Bax and activate the PI3K/Akt pathway, which may be the mechanism underlying anti-apoptosis of TAZ. All these findings indicated that TAZ acts as an oncogene that could be a key regulator of cell proliferation and apoptosis.