title: Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis.
abstract: By a proteomics-based approach, we identified an overexpression of fascin in colon adenocarcinoma cells (FPCKpP-3) that developed from nontumorigenic human colonic adenoma cells (FPCK-1-1) and were converted to tumorigenic by foreign-body-induced chronic inflammation in nude mice. Fascin overexpression was also observed in the tumors arising from rat intestinal epithelial cells (IEC 6) converted to tumorigenic in chronic inflammation which was induced in the same manner. Upregulation of fascin expression in FPCK-1-1 cells by transfection with sense fascin cDNA converted the cells tumorigenic, whereas antisense fascin-cDNA-transfected FPCKpP-3 cells reduced fascin expression and lost their tumor-forming ability in vivo. The tumorigenic potential by fascin expression was consistent with their ability to survive and grow in the three-dimensional multicellular spheroids. We found that resistance to anoikis (apoptotic cell death as a consequence of insufficient cell-to-substrate interactions), which is represented by the three-dimensional growth of solid tumors in vivo, was regulated by fascin expression through caspase-dependent apoptotic signals. From these, we demonstrate that fascin is a potent suppressor to caspase-associated anoikis and accelerator of the conversion of colonic adenoma cells into adenocarcinoma cells by chronic inflammation.
authors.affiliation: Division of Pathological Biochemistry, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kanda
authors.forename: Tokuichi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuramitsu
authors.forename: Takao
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Tokushige
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Norihiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.forename: Hasem
authors.initials: H
authors.lastname: Habelhah
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Mio
authors.initials: M
authors.lastname: Hirahata
authors.forename: Kunishige
authors.initials: K
authors.lastname: Onuma
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Osaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Masuo
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
mesh_terms: D000818:Animals; D023102:Anoikis / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018874:Spheroids, Cellular / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; C020324:fascin
keywords: Anoikis; Cell biology; Colon carcinogenesis; Fascin