PAK-dependent regulation of actin dynamics in breast cancer cells.

Metastatic Breast Cancer has a poor 25% survival rate and currently there are no clinical therapeutics which target metastasis. 'Migrastatics' are a new drug class which target migration pathway effector proteins in order to inhibit cancer cell invasion and metastasis. The p21-activated kinases (PAKs) are essential drivers of breast cancer cell migration and invasion through their regulation of actin cytoskeletal dynamics. Therefore, the PAKs present as attractive migrastatic candidates. Here we review how PAKs regulate distinct aspects of breast cancer actin dynamics focussing on cytoskeletal reorganisation, cell:matrix adhesion, actomyosin contractility and degradative invasion. Lastly, we discuss the introduction of PAK migrastatics into the well-honed breast cancer clinical pipeline.