The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression
生物
细胞生物学
细胞粘附
癌症研究
细胞迁移
下调和上调
细胞
遗传学
基因
作者
Katherine A. Young,Katarzyna Wojdyła,Tiffany Lai,Katie E Mulholland,Silvia Casanova,Robin Antrobus,Simon Andrews,Laura Biggins,Betania Mahler‐Araujo,P. Barton,Keith R. Anderson,Gareth W. Fearnley,Hayley J. Sharpe
ABSTRACT PTPRK is a receptor tyrosine phosphatase that is linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell–cell contact. PTPRK regulates cell–cell adhesion but is also reported to regulate numerous cancer-associated signalling pathways. However, the signalling mechanism of PTPRK remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling.