Signaling inputs to invadopodia and podosomes

Abstract

SummaryRemodeling of extracellular matrix (ECM) is a fundamental cell property that allows cells to alter their microenvironment and move through tissues. Invadopodia and podosomes are subcellular actin-rich structures that are specialized for matrix degradation and are formed by cancer and normal cells, respectively. Although initial studies focused on defining the core machinery of these two structures, recent studies have identified inputs from both growth factor and adhesion signaling as crucial for invasive activity. This Commentary will outline the current knowledge on the upstream signaling inputs to invadopodia and podosomes and their role in governing distinct stages of these invasive structures. We discuss invadopodia and podosomes as adhesion structures and highlight new data showing that invadopodia-associated adhesion rings promote the maturation of already-formed invadopodia. We present a model in which growth factor stimulation leads to phosphoinositide 3-kinase (PI3K) activity and formation of invadopodia, whereas adhesion signaling promotes exocytosis of proteinases at invadopodia.

Platelet-Derived Growth Factor Receptor Activation Promotes the Prodestructive Invadosome-Forming Phenotype of Synoviocytes from Patients with Rheumatoid Arthritis

“…Because invadosomes are transient dynamic structures, some areas of gelatin degradation were observed that were no longer associated with invadosome markers at the time of fixation. Together, these results indicate that synovial cells of arthritis patients produce typical invadosome structures similar to those produced by cancer cells or synovial cells from collagen-induced arthritis rats (5,42,43).…”

The interplay between the proteolytic, invasive, and adhesive domains of invadopodia and their roles in cancer invasion

“…72 Actin polymerization in the core of invadopodia is regulated by small Rho-family GTPases, mostly, CDC42, 1,28 which can directly activate the N-WASP-WIP complex, which, in turn, drives actin polymerization by the Arp2/3 complex. [73][74][75][76] Arp 2/3 actin nucleation is promoted by the severing activity of cofillin. [77][78][79] Additional reports indicate that actin polymerization in invadopodia of certain cancer cells (e.g., MDA-231 breast cancer cell line) can also be induced by specific Diaphanous-related formins, whose cell type specificity, and mode of action and regulation, are still unclear.…”

IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

“…During tumor invasion, GBM cells from the tumor migrate towards the neighbouring normal tissue by extending their edge actin-rich cancer-specific membrane protrusions forming invadopodia with the ability to infiltrate and degrade physical barriers, such as basement membranes, extracellular matrix (ECM), and cell junctions by metalloproteinases (MMPs) [30,35,36]; podosome/invadopodia are identified for their high expression levels of F-actin and/or cortactin [46]. The role of IQGAP1 as a scaffold protein in the delivering process of MMPs has been demonstrated in cell lines and animal models, as C. elegans, zebrafish, sea squirt, mice and rat [33,40,47,48]. Figure 7 is a simplified model of some of the proteins involved in the podosome/invadopodia generation mechanism and a model of the involvement of IQGAP1 in GBM progression based on the present study.…”