RAB5A promotes the formation of filopodia in pancreatic cancer cells via the activation of cdc42 and β1-integrin

Filopodia are slender actin-rich plasma membrane protrusions that function to drive cell migration and invasion. Despite the observation of defective filopodia formation in many malignant tumors, the regulation mechanism remained unknown to date. In the present study, for the first time, we demonstrate that RAB5A, a Rab GTPase family protein, is a potent regulator of filopodia formation in pancreatic cancer cells. High expression of RAB5A was associated with filopodia formation and migration in pancreatic cancer cells. Overexpression of RAB5A promoted filopodia formation and migration in CF Pact cells. In contrast, down-regulation of RAB5A expression in SW1990 cells with a high endogenous RAB5A expression level impeded the formation of filopodia. Further analysis indicated that RAB5A was required for cdc42 activation in CF Pac-1 and SW1990 cells. Moreover, to investigate the underlying mechanism by which the activation of cdc42 mediates RAB5A-induced filopodia formation, the active state of beta 1-integrin was examined in cells with different expression levels of RAB5A. We observed that RAB5A regulated the accumulation of the active beta 1-integrin. We demonstrated that down-regulation of the expression of beta 1-integrin strongly suppressed filopodia formation and cdc42 activation mediated by RAB5A. These results indicate the important role of RAB5A in the regulation of filopodia formation in pancreatic cancer cells, which is dependent on the activation of cdc42 and beta 1-integrin. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

RAB5A is identified as a potent regulator of filopodia formation in pancreatic cancer cells, with its high expression associated with filopodia formation and cell migration. The mechanism involves the activation of cdc42 and regulation of beta 1-integrin by RAB5A to promote filopodia formation.