Differential roles of cyclin–CDK1 complexes in cell migration and invasion

Abstract

We have previously described a central role for CDK1 at the nexus of adhesion signalling and cell cycle progression, demonstrating that CDK1 has a non-canonical role in regulating integrin adhesion complexes and in the migration of cancer cells in 3D interstitial matrix. Here, we show that the CDK1-binding partners cyclinB1 and cyclinA2 also have roles in cell migration and invasion in both cancer and non-transformed cells. CyclinB1 plays a key role in RhoA activation to promote rear retraction in a membrane tension-dependent manner, whereas cyclinA2 has a general role in promoting motility. Knockdown of either cyclin significantly perturbs migration with contrasting phenotypes, whereas knockdown of both together has an additive effect, which arrests both migration and division. Our findings therefore describe how cyclin–CDK1 complexes orchestrate migration as well as division of cells, and that cyclinA2–CDK1 and cyclinB1–CDK1 complexes play distinct roles in motility.