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: 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
• Journal: Proteomics (Proteomics) Vol. 14 Issue 9 Pg. 1031-41 (May 2014) ISSN: 1615-9861 [Electronic] Germany
• PMID: 24574163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Carrier Proteins
• Microfilament Proteins
• fascin

Topics

• Animals
• Anoikis (physiology)
• Carrier Proteins (analysis, genetics, metabolism)
• Cell Line, Tumor
• Colonic Neoplasms (metabolism)
• Female
• Humans
• Inflammation (metabolism)
• Mice
• Mice, Nude
• Microfilament Proteins (analysis, genetics, metabolism)
• Rats
• Spheroids, Cellular (metabolism)
• Tumor Cells, Cultured (metabolism)