WBP2 PROMOTES GASTRIC CANCER CELL MIGRATION BY INHIBITING THE HIPPO SIGNALLING PATHWAY

Abstract

Aberrant tyrosine kinase activity and signalling pathways have been implicated in gastric cancer (GC). To map the molecular changes in GC, iTRAQ/LC-MS/MS-based phosphoproteomics analysis was performed. A total of 530 proteins with altered phosphorylation levels were detected across a panel of 15 gastric cell lines (1 normal and 14 cancer). WBP2, a novel GC associated protein was selected for further studies. Clinically, WBP2 is overexpressed in GC tissues and its expression level correlates with poor clinical outcome. Depletion of WBP2 decreased GC cell migration, concomitant with activation of LATS activity, increased YAP phosphorylation, decreased YAP/TEAD reporter activity and expression of TEAD target genes such as CTGF and CYR61. Silencing LATS rescued migration in WBP2-depleted cells, demonstrating the interplay between WBP2 and LATS kinases in the regulation of GC cell migration. Mechanistically, WBP2 was found to interact with LATS. Preliminary evidence consisting of a screen for potential mediators between WBP2 and LATS have also indicated that HGK and/or NF2 may play a role in mediating the effect of WBP2 on LATS activity. In conclusion, WBP2 plays a pivotal role in the regulation of GC cell migration via the Hippo pathway transducer LATS.