Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis

Yusuke Kanda, Tokuichi Kawaguchi, Yasuhiro Kuramitsu, Takao Kitagawa, Tokushige Kobayashi, Norihiko Takahashi, Hiroshi Tazawa, Hasem Habelhah, Jun Ichi Hamada, Masanobu Kobayashi, Mio Hirahata, Kunishige Onuma, Mitsuhiko Osaki, Kazuyuki Nakamura, Tomoyuki Kitagawa, Masuo Hosokawa, Futoshi Okada

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1031-1041
Number of pages11
JournalProteomics
Volume14
Issue number9
DOIs
Publication statusPublished - May 2014

Keywords

  • Anoikis
  • Cell biology
  • Colon carcinogenesis
  • Fascin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Kanda, Y., Kawaguchi, T., Kuramitsu, Y., Kitagawa, T., Kobayashi, T., Takahashi, N., Tazawa, H., Habelhah, H., Hamada, J. I., Kobayashi, M., Hirahata, M., Onuma, K., Osaki, M., Nakamura, K., Kitagawa, T., Hosokawa, M., & Okada, F. (2014). Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis. Proteomics, 14(9), 1031-1041. https://doi.org/10.1002/pmic.201300414