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J Cell Sci ; 137(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38904097

RESUMEN

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.


Asunto(s)
Transición Epitelial-Mesenquimal , Humanos , Animales , Ratones , Receptores ErbB/metabolismo , Receptores ErbB/genética , Transducción de Señal , Adhesión Celular/genética , Movimiento Celular , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Colitis/patología , Colitis/metabolismo , Colitis/genética , Colitis/inducido químicamente , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/metabolismo , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética , Intestinos/patología
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