Analysis of molecular mechanisms for the filamin-induced defensive force of normal epithelial cells against cancer

• Project/Area Number: 26870004
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology; Tumor biology
• Research Institution: Tokyo Medical and Dental University (2015); Hokkaido University (2014)
• Principal Investigator: Kajita Mihoko 東京医科歯科大学, 難治疾患研究所, プロジェクト助教 (00607442)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: filamin / EDAC / SILAC / Caveolin / EPLIN / S1P / Filamin / apical extrusion

Outline of Final Research Achievements

Normal epithelial cells recognize and extrude neighboring transformed cells from an epithelial monolayer. We named this process as EDAC (Epithelial Defense Against Cancer). In this project, I focused on filamin, which plays a central role for EDAC, to understand molecular mechanisms for EDAC. Several molecules were successfully identified as increased binding to filamin under the mix culture of normal and transformed cells. Furthermore, the interaction between newly identified EDAC-inducing molecules and filamin was also elucidated.

Research Products

• [Journal Article] A role of the sphingosine-1-phosphate (S1P)- S1P receptor 2 pathway in Epithelial Defense Against Cancer (EDAC) (2015)
  • Author(s): Yamamoto, S., Yako, Y., Fujioka, Y., Kajita, M., Kameyama, T., Kon, S., Ishikawa, S., Ohba, Y., Ohno, Y., Kihara, A., and Fujita, Y.
  • Journal Title: Molecular Biology of the Cell Volume: 27（3） Issue: 3 Pages: 491-499
  • DOI: 10.1091/mbc.e15-03-0161
  • NAID: 120005740332
  • Peer Reviewed / Open Access
• [Journal Article] EDAC (Epithelial defence against cancer) -cell competition between normal and transformed epithelial cells in mammals. (2015)
  • Author(s): Kajita, M. and Fujita, Y.
  • Journal Title: 実験医学（増刊） Volume: 33 Pages: 128-134
  • NAID: 40020522502
• [Journal Article] EDAC: Epithelial defence against cancer- cell competition between normal and transformed epithelial cells in mammals. (2015)
  • Author(s): Kajita, M. and Fujita, Y.
  • Journal Title: Journal of Biochemistry Volume: 158(1) Issue: 1 Pages: 15-23
  • DOI: 10.1093/jb/mvv050
  • NAID: 40020522502
  • Peer Reviewed / Open Access
• [Journal Article] EPLIN is a crucial regulator for extrusion of RasV12-transformed cells. (2015)
  • Author(s): Ohoka, A., Kajita, M., Ikenouchi, J., Yako, Y., Kitamoto, S., Kon, S., Ikegawa, M., Shimada, T., Ishikawa, S., and Fujita, Y.
  • Journal Title: Journal of Cell Science Volume: 128 Pages: 781-789
  • DOI: 10.1242/jcs.163113
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Filamin acts as a key regulator in epithelial defence against transformed cells. (2014)
  • Author(s): Kajita M., Sugimura, K., Ohoka, A., Burden, J., Suganuma, H., Ikegawa, M., Shimada, T., Kitamura, T., Shindoh, M., Ishikawa, S., Yamamoto, S., Saitoh, S., Yako, Y., Takahashi, R., Okajima, T., Kikuta, J., Maijima, Y., Ishii, M., Tada, M., and Fujita, Y.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 4428-4428
  • DOI: 10.1038/ncomms5428
  • Peer Reviewed / Open Access
• [Presentation] Filamin acts as a key regulator in epithelial defense against transformed cells (2014)
  • Author(s): Mihoko Kajita
  • Organizer: 第３７回分子生物学会
  • Place of Presentation: パシフィコ横浜 （神奈川県・横浜市）
  • Year and Date: 2014-11-25