PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.
Protein Tyrosine Kinase 6 (PTK6) is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each). In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05). Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.
Department of Surgery, Michigan State University, College of Human Medicine, East Lansing, Michigan, United States of America.
Hiroaki
H
Ono
Department of Surgery, Michigan State University, College of Human Medicine, East Lansing, Michigan, United States of America.
Marc D
MD
Basson
Department of Surgery, Michigan State University, College of Human Medicine, East Lansing, Michigan, United States of America.
Hiromichi
H
Ito
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human