Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration

• DOI: 10.1242/jcs.150987
• Publication Date: 2014-07-12T04:52:31Z
• Authors: Philippe Gui; Arnaud Labrousse; Emeline Van Goethem; Arnaud Besson; Isabelle Maridonn...; Véronique Le Cabec
• Keywords: CDK inhibitor

Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted certain cells. Here, we investigated initiating mechanisms involved in macrophage MM. We show that a single is able use both modes. MM correlated with decreased Rho/Rho-associated protein kinase (ROCK) activity potentiated by ROCK inhibition, suggesting AM inhibition could participate mechanisms. identify cyclin-dependent (CDK) inhibitor p27kip1 as new effector of 3D-migration. Using siRNA mutant mice, promotes hinders upstream Rho/ROCK pathway, process associated relocation from nucleus cytoplasm. Finally, observe cytoplasmic required for vivo induced tumours mice. This study provides first evidence silencing through pathway participates onset