title: Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis.
abstract: To investigate the molecular mechanisms of cancer metastasis, we have isolated a high-metastatic bladder cancer cell subpopulation from a low-metastatic cell line by using an in vivo selection system. Cells in the subpopulation showed a high ability to form invadopodia, the filamentous actin (F-actin)-based membrane protrusions that play an essential role in cancer cell invasion. Analysis of the gene expression profile revealed that the expression of an intermediate filament (IF) protein, vimentin and a cytoskeletal linker protein, plectin was up-regulated in the high-metastatic subpopulation compared with the low metastatic cell line. Here we report a novel role of vimentin IF and plectin in metastasis. In invasive bladder cancer cells, the vimentin IF-plectin-invadopodia F-actin link was formed. Disruption of this link severely impaired invadopodia formation, reducing the capacities of extracellular matrix degradation, transendothelial migration and metastasis. In addition, the vimentin assembly into the filaments was required for invadopodia formation. Our results suggest that plectin anchoring invadopodia to vimentin IF scaffolds and stabilizes invadopodia, which is a critical molecular process for cancer cell invasion and extravasation for metastasis.
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Sutoh Yoneyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.affiliation: Department of Urology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Cancer Immunology and Cell Biology, Oyokyo Kidney Research Institute, Hirosaki, Japan.
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Funyu
authors.affiliation: Max F. Perutz Laboratories, Department of Biochemistry and Cell Biology, University of Vienna, Vienna 1030, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wiche
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Department of Cancer Immunology and Cell Biology, Oyokyo Kidney Research Institute, Hirosaki, Japan. Electronic address: urology@cc.hirosaki-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuboi
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D051190:Plectin / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D051190:Plectin; D014746:Vimentin
keywords: Cancer cell extravasation; Invadopodium; Invadosome; Invasion; Plectin; Vimentin