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

11 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 - 2014

Fingerprint

Anoikis
Colon
Carcinogenesis
Inflammation
Tumors
Caspases
Adenoma
Adenocarcinoma
Complementary DNA
Cellular Spheroids
fascin
Neoplasms
Cell death
Foreign Bodies
Nude Mice
Proteomics
Particle accelerators
Transfection
Rats
Cell Death

Keywords

  • Anoikis
  • Cell biology
  • Colon carcinogenesis
  • Fascin

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Medicine(all)

Cite this

Kanda, Y., Kawaguchi, T., Kuramitsu, Y., Kitagawa, T., Kobayashi, T., Takahashi, N., ... 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

Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis. / Kanda, Yusuke; Kawaguchi, Tokuichi; Kuramitsu, Yasuhiro; Kitagawa, Takao; Kobayashi, Tokushige; Takahashi, Norihiko; Tazawa, Hiroshi; Habelhah, Hasem; Hamada, Jun Ichi; Kobayashi, Masanobu; Hirahata, Mio; Onuma, Kunishige; Osaki, Mitsuhiko; Nakamura, Kazuyuki; Kitagawa, Tomoyuki; Hosokawa, Masuo; Okada, Futoshi.

In: Proteomics, Vol. 14, No. 9, 2014, p. 1031-1041.

Research output: Contribution to journalArticle

Kanda, Y, Kawaguchi, T, Kuramitsu, Y, Kitagawa, T, Kobayashi, T, Takahashi, N, Tazawa, H, Habelhah, H, Hamada, JI, 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, vol. 14, no. 9, pp. 1031-1041. https://doi.org/10.1002/pmic.201300414
Kanda Y, Kawaguchi T, Kuramitsu Y, Kitagawa T, Kobayashi T, Takahashi N et al. Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis. Proteomics. 2014;14(9):1031-1041. https://doi.org/10.1002/pmic.201300414
Kanda, Yusuke ; Kawaguchi, Tokuichi ; Kuramitsu, Yasuhiro ; Kitagawa, Takao ; Kobayashi, Tokushige ; Takahashi, Norihiko ; Tazawa, Hiroshi ; Habelhah, Hasem ; Hamada, Jun Ichi ; Kobayashi, Masanobu ; Hirahata, Mio ; Onuma, Kunishige ; Osaki, Mitsuhiko ; Nakamura, Kazuyuki ; Kitagawa, Tomoyuki ; Hosokawa, Masuo ; Okada, Futoshi. / Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis. In: Proteomics. 2014 ; Vol. 14, No. 9. pp. 1031-1041.
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