Effects of MST1/2 Kinase Inhibitor XMU-MP-1 on the Hippo Signaling Pathway and Bovine Granulosa Cell Function

Abstract

The Hippo signaling pathway is an evolutionarily conserved pathway which is important for organ size control and cell proliferation. The pathway’s role in tumorigenesis has been well-studied, but its importance in reproduction is emerging. Recent studies highlighted the significance of the pathway’s components, YAP1 and TAZ, on granulosa cell function and proliferation. This present study investigated the effects of chemical inhibition of MST1/2 by a known inhibitor, XMU-MP-1, on bovine granulosa cells. There were significant increases in the mRNA expression levels of LATS1, LATS2, and TEAD4 after a 12-hour XMU-MP-1 treatment period, along with decreased protein expression of total p-YAP1 and cytoplasmic levels of p-YAP1, YAP1, and TAZ proteins. However, no significant changes were detected in the nuclear protein levels and the assessed granulosa cell functional and proliferation markers. Overall, MST1/2 inhibition by XMU-MP-1 resulted in alterations to components of the Hippo signaling pathway without affecting bovine granulosa cell function and proliferation.