The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.

Autor:	Young KA; Signalling programme, Babraham Institute, Cambridge CB22 3AT, UK., Wojdyla K; Signalling programme, Babraham Institute, Cambridge CB22 3AT, UK., Lai T; Signalling programme, Babraham Institute, Cambridge CB22 3AT, UK., Mulholland KE; Signalling programme, Babraham Institute, Cambridge CB22 3AT, UK., Aldaz Casanova S; Signalling programme, Babraham Institute, Cambridge CB22 3AT, UK., Antrobus R; Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 0XY, UK., Andrews SR; Bioinformatics, Babraham Institute, Cambridge CB22 3AT, UK., Biggins L; Bioinformatics, Babraham Institute, Cambridge CB22 3AT, UK., Mahler-Araujo B; Histopathology, Cambridge University Hospitals, Cambridge CB2 0QQ, UK., Barton PR; Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 0XY, UK., Anderson KR; Molecular biology department, Genentech, South San Francisco, CA 94080, USA., Fearnley GW; Signalling programme, Babraham Institute, Cambridge CB22 3AT, UK., Sharpe HJ; Signalling programme, Babraham Institute, Cambridge CB22 3AT, UK.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2024 Jul 15; Vol. 137 (14). Date of Electronic Publication: 2024 Jul 22.
DOI:	10.1242/jcs.261914
Abstrakt:	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. Competing Interests: Competing interests K.R.A. is an employee of Genentech, a member of the Roche Group. All other authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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