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.

PurposeThe aim of the present study was to investigate the effect of knockdown and knockout of the transcriptional co-activator with PDZ-binding motif (TAZ) on the migration, invasion and autophagy of the hepatocellular carcinoma (HCC) cell lines, as well as the functional connection between the autophagy and cell migratory processes induced by loss of TAZ in HCC cell lines.MethodsHCC cell lines SMMC-7721 and SK-HEP1 stably knockdown and knockout of TAZ were established by the lentiviral-mediated TAZ knockdown and knockout approaches. Reverse transcription-quantitative real-time polymerase chain reaction and Western blotting were performed to examine the expression of TAZ and indicated genes in downstream pathways in HCC cell lines. Transwell assay and autophagic flux assay were used to evaluate the effect of TAZ knockdown and knockout on the motility and the autophagy of HCC cell lines.ResultsWe initially found that TAZ exhibited highly abundant and was expressed predominantly in HCC cell lines with different spontaneous metastatic potential. Through performing loss-of-function assays, we demonstrated that both TAZ knockdown and knockout promoted HCC cell autophagy and reduced HCC cell migration, invasion and epithelial-to-mesenchymal transition. In addition, autophagy inhibition in TAZ knockdown and knockout SMMC-7721 and SK-HEP1 cells in the presence of 3-methyladenine or chloroquine partially abrogated the migratory and invasive ability induced by TAZ knockdown and knockout.ConclusionOur findings indicated that loss of TAZ in HCC cells suppressed cell motility probably via altering the autophagy, suggesting that TAZ emerges as an important target in regulating cell motility and autophagy in HCC cells, and blocking TAZ may be a novel therapeutic strategy against HCC.