Monopolar spindle-one-binder protein 2 regulates the activity of large tumor suppressor/yes-associated protein to inhibit the motility of SMMC-7721 hepatocellular carcinoma cells.

ABSTRACT

Accumulating evidence implicates monopolar spindle-one-binder protein (MOB)2 as an inhibitor of nuclear-Dbf2-related kinase (NDR) by competing with MOB1 for interaction with NDR1/2. NDR/large tumor suppressor (LATS) kinases may function similarly to yes-associated protein (YAP) kinases and be considered as members of the Hippo core cassette. MOB2 appears to serve roles in cell survival, cell cycle progression, responses to DNA damage and cell motility. However, the underlying mechanisms involved remain unclarified. In the present study, it was demonstrated that the knockout of MOB2 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 promoted migration and invasion, induced phosphorylation of NDR1/2 and decreased phosphorylation of YAP in SMMC-7721 cells when compared with the blank vector-transduced cells. By contrast, the overexpression of MOB2 resulted in the opposite results. Mechanistically, MOB2 regulated the alternative interaction of MOB1 with NDR1/2 and LATS1, which resulted in increased phosphorylation of LATS1 and MOB1 and thereby led to the inactivation of YAP and consequently inhibition of cell motility. The results of the present study provide evidence of MOB2 serving a positive role in LATS/YAP activation by activating the Hippo signaling pathway.