N-WASP-mediated invadopodium formation is involved in intravasation and lung metastasis of mammary tumors

• DOI: 10.1242/jcs.092726
• Publication Date: 2012-03-05T16:11:08Z
• Authors: Bojana Gligorijevic; Jeffrey Wyckoff; Hideki Yamaguchi; Yarong Wang; Evanthia T. Roussos; John Condeelis
• Keywords: Invadopodia; Intravasation; Podosome

Invadopodia are proteolytic membrane protrusions formed by highly invasive cancer cells, commonly observed on substrate(s) mimicking extracellular matrix. Although invadopodia proposed to have roles in invasion and metastasis, direct evidence has not been available. We previously reported that neural Wiskott–Aldrich syndrome protein (N-WASP), a member of WASP family proteins regulate reorganization the actin cytoskeleton, is an essential component invadopodia. Here, we report N-WASP-mediated invadopodium formation breast invasion, intravasation lung metastasis. established stable cell lines based MTLn3 rat mammary adenocarcinoma cells either overexpressed dominant-negative (DN) N-WASP construct or which expression was silenced pSuper shRNA. Both shRNA DN showed markedly decreased ability form degrade In addition, primary tumors collagen I degradation were reduced areas (collagen-rich edge tumor) (blood-vessel-rich areas). Our results suggest tumor vivo activity also invadopodia, migrate, invade, intravasate disseminate compared with parental levels.