LATS2 Inhibits Malignant Behaviors of Glioma Cells via Inactivating YAP

We previously reported that LATS2, the upstream serine/threonine kinase of Yes-associated protein (YAP), is downregulated in gliomas and exhibits negative correlation with the prognosis of glioma patients. In this work, we aimed to explore the role and mechanism of large tumor suppressor kinase (LATS2) in the progression of malignant gliomas. We found that over-expression of LATS2 inhibited glioma cell proliferation and migration/invasion, while LATS2 downregulation promoted them. Mechanistically, LATS2 promoted the phosphorylation of YAP without affecting YAP mRNA expression. Inconsistent with some previous reports, both YAP(WT) and YAP(5SA) did not affect the level of LATS2, suggesting that LATS2 did not form a feedback loop with YAP in gliomas. Furthermore, mammalian Ste20-like kinases (MST1) over-expression did not affect the phosphorylation of YAP, suggesting that MST1 may not be the essential upstream serine/threonine kinase of Hippo/YAP pathway in gliomas. Together, LATS2 inhibits glioma cell proliferation and migration/invasion by inactivating YAP.