WIP: WASP-interacting proteins at invadopodia and podosomes

Abstract

Regulated cell invasion resulting from migratory and matrix-degrading events is an essential step in physiological processes such as the inflammatory response and tissue repair. Cell invasion is also thought to be a critical parameter in pathological conditions such as cancer metastasis. The migration of normal and cancer cells is largely driven by the actin cytoskeleton, which controls cell shape, adhesion and contractility. Podosomes and invadopodia are actin-rich protrusions that drive invasion in normal and cancer cells. These structures protrude from the basal region of the cell facing the extracellular matrix, where they adhere to and degrade the matrix, thus facilitating invasive migration. WASP (Wiskott–Aldrich syndrome protein) and WIP (WASP-interacting protein) localise to the actin rich core of podosomes and play a critical role in their formation. More recently, studies performed on microarray data sets from cancer patients of several tumour categories show a strong correlation between reduced WIP expression and improved prognosis. In this article, we identify endogenous WIP at the distal tips of cancer cell invasive protrusions and we summarise recent advances in the study of the roles of WIP- and WASP-protein families during migration and invasion of normal and cancer cells related to podosome and invadopodium generation.