TSSK1β inhibits the Hippo pathway effector protein YAP to suppress cell proliferation

Abstract

The Hippo signaling pathway, which is involved in the regulation of cell proliferation, and an important tumor suppressor. The central regulators of the Hippo signaling pathway include the transcriptional co-activators YAP /TAZ which are negatively regulated by LATS1/2 kinases. The phosphorylation of YAP/TAZ promote their cytoplasmic sequestration where they bind with 14-3-3 protein or undergo proteasomal degradation. Dysregulation of Hippo pathway promotes the oncogenic properties of YAP/TAZ and improves cancer progression. However, the potential of YAP as a therapeutic target for cancer has not been well studied. To identify kinases-induced the phosphorylation of YAP, we screened diverse kinases which belong to CAMK family. This study demonstrated that TSSK1β promoted YAP phosphorylation partially through the LATS1/2-dependent or –independent mechanisms. Furthermore, TSSK1β consequently inhibits cell proliferation and anchorage-independent growth in LATS1/2 DKO MEFs. In summary, our findings suggest that TSSK1β can suppress YAP/TAZ-mediated cancer cell proliferation. Thus, TSSK1β can be a potential therapeutic target carcinogenesis.