title: Dynamin2 GTPase contributes to invadopodia formation in invasive bladder cancer cells.
abstract: Cancer cell invasion is mediated by actin-based membrane protrusions termed invadopodia. Invadopodia consist of "core" F-actin bundles associated with adhesive and proteolytic machineries promoting cell invasion by degrading extracellular matrix (ECM). Formation of the F-actin core in invadopodia is regulated by various actin-binding proteins including Arp2/3 complex and cortactin. Dynamin GTPase localizes to the invadopodia and is implicated in cancer cell invasion, but its precise role at the invadopodia remained elusive. In this study, we examined the roles of dynamin at the invadopodia of bladder cancer cells. Although all three dynamin isoforms (dynamin1, 2 and 3) are expressed in human bladder cancer cell line T24, only dynamin2 localizes to the invadopodia. Inhibition of dynamin2 function, using either RNA interference (RNAi) or the dynamin specific inhibitor Dynasore, caused defects in invadopodia formation and suppressed invasive activity of T24 bladder cancer cells. Structure-function analysis using dynamin2 deletion fragments identified the proline/arginine-rich domain (PRD) of dynamin2 as indispensable for invadopodia formation and invasiveness of T24 cells. Thus, dynamin2 contributes to bladder cancer invasion by controlling invadopodia formation in bladder cancer cells and may prove a valuable therapeutic target.
authors: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan.
authors: Yubai
authors: Y
authors: Zhang
authors: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan.
authors: Maya
authors: M
authors: Nolan
authors: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan.
authors: Hiroshi
authors: H
authors: Yamada
authors: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan.
authors: Masami
authors: M
authors: Watanabe
authors: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan.
authors: Yasutomo
authors: Y
authors: Nasu
authors: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan. Electronic address: kohji@md.okayama-u.ac.jp.
authors: Kohji
authors: K
authors: Takei
authors: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Kita-ku, Okayama 700-8558, Japan. Electronic address: ttakeda@okayama-u.ac.jp.
authors: Tetsuya
authors: T
authors: Takeda
mesh_terms: D001665:Binding Sites; D049108:Cell Enlargement; D045744:Cell Line, Tumor; D034285:Dynamin II; D034281:Dynamins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D000069261:Podosomes / Q000201:enzymology* / Q000473:pathology*; D011485:Protein Binding; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D020558:GTP Phosphohydrolases; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins
keywords: Actin; Bladder cancer; Cortactin; Dynamin; Invadopodia