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Fascin regulates chronic inflammation‐related human colon carcinogenesis by inhibiting cell anoikis
Author(s) -
Kanda Yusuke,
Kawaguchi Tokuichi,
Kuramitsu Yasuhiro,
Kitagawa Takao,
Kobayashi Tokushige,
Takahashi Norihiko,
Tazawa Hiroshi,
Habelhah Hasem,
Hamada Junichi,
Kobayashi Masanobu,
Hirahata Mio,
Onuma Kunishige,
Osaki Mitsuhiko,
Nakamura Kazuyuki,
Kitagawa Tomoyuki,
Hosokawa Masuo,
Okada Futoshi
Publication year - 2014
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300414
Subject(s) - fascin , anoikis , cancer research , carcinogenesis , inflammation , apoptosis , cell , microbiology and biotechnology , biology , transfection , downregulation and upregulation , programmed cell death , cell culture , immunology , cancer , biochemistry , actin , genetics , gene
By a proteomics‐based approach, we identified an overexpression of fascin in colon adenocarcinoma cells ( FPCK pP‐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 c DNA converted the cells tumorigenic, whereas antisense fascin‐c DNA ‐transfected FPCK pP‐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.