Molecular mechanism for collective invasion of cancer cell groups

• Project/Area Number: 23701051
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Nagoya University
• Principal Investigator: KATO Takuya 名古屋大学, 医学系研究科, 助教 (00551970)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: collective invasion / がん / 浸潤 / Collective migration / RFP / MRTF / integrin

Research Abstract

We revealed that expression of integrin β1 is up-regulated in leading cells compared to trailing cells. Increase of integrin β1 expression is crucial for effective migration in cells moving as a group. Two transcriptional regulators, RET Finger Protein (RFP) and Myocardin Related Transcription Factor-B (MRTF-B), form complex responding to the partial loss of cell-cell adhesion in leading cells, which activate Rho GTPase, and up-regulates the integrin β1 expression through the repression of integrin β1-targetting microRNA-124 in LC. Our findings revealed the molecular mechanism that defines heterogenous properties of LC and FC.

Research Products

• [Journal Article] Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer (2013)
  • Author(s): An J, Enomoto A, Weng L, Kato T, Iwakoshi A, Ushida K, Maeda K, Ishida-Takagishi M, Ishii G, Ming S, Sun T, Takahashi M
  • Journal Title: J Cancer Res Clin Oncol Volume: 139(3) Pages: 379-88
  • Peer Reviewed
• [Journal Article] Metamorphosis of mesothelial cells with active horizontal motility in tissue culture (2013)
  • Author(s): Nagai H, Chew SH, Okazaki Y, Funahashi S, Namba T, Kato T, Enomoto A, Jiang L, Akatsuka S, Toyokuni S
  • Journal Title: Sci Rep Volume: 3 Issue: 1 Pages: 1144-1144
  • DOI: 10.1038/srep01144
  • Peer Reviewed
• [Journal Article] Significance of cancer-associatea fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer (2013)
  • Author(s): An J, Enomoto A, Weng L, et al.
  • Journal Title: J Cancer Res Clin Volume: 139 Issue: 3 Pages: 379-388
  • DOI: 10.1007/s00432-012-1328-6
  • Peer Reviewed
• [Journal Article] RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations (2012)
  • Author(s): Iwakoshi A, Murakumo Y, Kato T, Kitamura A, Mii S, Saito S, Yatabe Y, Takahashi M
  • Journal Title: Pathol Int Volume: 62(5) Pages: 324-30
  • NAID: 10031185208
  • Peer Reviewed
• [Journal Article] Involvement of Girdin in the determination of cell polarity during cell migration (2012)
  • Author(s): Ohara K, Enomoto A, et al.
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e36681-e36681
  • DOI: 10.1371/journal.pone.0036681
  • Peer Reviewed
• [Journal Article] The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility (2012)
  • Author(s): Ishida-Takagishi M, Enomoto A, et al.
  • Journal Title: Nat Commun Volume: 3 Issue: 1 Pages: 859-859
  • DOI: 10.1038/ncomms1861
  • Peer Reviewed
• [Journal Article] Epidermal hyperplasia and appendage abnormalities in mice lacking CD109 (2012)
  • Author(s): Mii S, Murakumo Y, Asai N, Jijiwa M, Hagiwara S, Kato T, Asai M, Enomoto A, Ushida K, Sobue S, Ichihara M, Takahashi M
  • Journal Title: Am J Pathol Volume: 181(4) Pages: 1180-9
  • Peer Reviewed
• [Journal Article] Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer (2012)
  • Author(s): Horio M, Kato T, Mii S, Enomoto A, Asai M, Asai N, Murakumo Y, Shibata K, Kikkawa F, Takahashi M
  • Journal Title: Cancer Med Volume: 1(2) Pages: 218-29
  • Peer Reviewed
• [Journal Article] Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer. (2012)
  • Author(s): Maiko Horio
  • Journal Title: Cancer Medicine Volume: 1 Issue: 2 Pages: 218-29
  • DOI: 10.1002/cam4.32
  • Peer Reviewed
• [Journal Article] RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations. (2012)
  • Author(s): Akari Iwakoshi
  • Journal Title: Pathol International Volume: 62 Issue: 5 Pages: 324-30
  • DOI: 10.1111/j.1440-1827.2012.02797.x
  • Peer Reviewed
• [Journal Article] Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb1. (2012)
  • Author(s): Kee HJ, Kim JR, Joung H, Choe N, Lee SE, Eom GH, Kim JC, Geyer SH, Jijiwa M, Kato T, Kawai K, Weninger WJ, Seo SB, Nam KI, Jeong MH, Takahashi M, Kook H.
  • Journal Title: Cell Death Differentiation Volume: 19 Pages: 121-31
  • Peer Reviewed
• [Journal Article] Analysis of glial cell line-derived neurotrophic factor-inducible zinc finger protein 1 expression in human diseased kidney (2011)
  • Author(s): Saito S, Murakumo Y, Tsuzuki T, Dambara A, Kato T, Enomoto A, Asai N, Maruyama S, Matsuo S, Takahashi M
  • Journal Title: Hum Pathol Volume: 42(6) Pages: 848-58
  • Peer Reviewed
• [Journal Article] An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors (2011)
  • Author(s): Motegi Y, Katayama K, Sakurai F, Kato T, Yamaguchi T, Matsui H, Takahashi M, Kawabata K, Mizuguchi H
  • Journal Title: J Control Release Volume: 153(2) Pages: 149-53
  • Peer Reviewed
• [Journal Article] Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain (2011)
  • Author(s): Wang Y, Kaneko N, Asai N, Enomoto A, Isotani-Sakakibara M, Kato T, Asai M, Murakumo Y, Ota H, Hikita T, Namba T, Kuroda K, Kaibuchi K, Ming GL, Song H, Sawamoto K, Takahashi M
  • Journal Title: J Neurosci Volume: 31(22) Pages: 8109-22
  • Peer Reviewed
• [Journal Article] Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain. (2011)
  • Author(s): Wang Y, Kaneko N, Asai N, Enomoto A, Isotani-Sakakibara M, Kato T, Asai M, Murakumo Y, Ota H, Hikita T, Namba T, Kuroda K, Kaibuchi K, Ming GL, Song H, Sawamoto K, Takahashi M.
  • Journal Title: Journal of Neuroscience Volume: 31 Pages: 8109-22
  • Peer Reviewed
• [Journal Article] An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors. (2011)
  • Author(s): Motegi Y, Katayama K, Sakurai F, Kato T, Yamaguchi T, Matsui H, Takahashi M, Kawabata K, Mizuguchi H.
  • Journal Title: Journal of Control Release Volume: 153 Pages: 149-53
  • Peer Reviewed
• [Journal Article] Analysis of glial cell line-derived neurotrophic factor-inducible zinc finger protein 1 expression in human diseased kidney. (2011)
  • Author(s): Saito S, Murakumo Y, Tsuzuki T, Dambara A, Kato T, Enomoto A, Asai N, Maruyama S, Matsuo S, Takahashi M.
  • Journal Title: Human pathology Volume: 42 Pages: 848-58
  • Peer Reviewed
• [Presentation] Regulatory mechanism of integrin beta1 expression in collectively migrating cancer cells (2013)
  • Author(s): Kato, T., Enomoto, A., Asai, M., Asai, N., Takahashi, M
  • Organizer: 9th AACR-JCA Joint Meeting
  • Place of Presentation: ハワイ、アメリカ合衆国
  • Year and Date: 2013-02-23
• [Presentation] Regulatory mechanism of integrin beta1 expression in collectively migrating cancer cells (2012)
  • Author(s): Kato, T., Enomoto, A., Haga, H., Ishida, S., Asai, M., Asai, N., Takahashi, M.
  • Organizer: The American Society of Cell Biology, 2012 Annual Meeting
  • Place of Presentation: サンフランシスコ、アメリカ合衆国
  • Year and Date: 2012-12-18
• [Presentation] Regulatory mechanism of integrin beta1 expression in collectively migrating cancer cells (2012)
  • Author(s): 加藤琢哉, 榎本篤, 浅井真人, 浅井直也, 村雲芳樹, 高橋雅英
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] がん細胞の集団的浸潤の制御機構の解析 (2012)
  • Author(s): 加藤琢哉, 榎本篤, 浅井直也, 村雲芳樹, 高橋雅英
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-28
• [Presentation] Cell-cell contact dependent regulatory role of RFP in integrin beta1 expression. (2011)
  • Author(s): Kato T, Enomoto A, Asai N, Murakumo Y, Takahashi M
  • Organizer: The American Society of Cell Biology, 2011 Annual Meeting
  • Place of Presentation: デンバー、アメリカ合衆国
  • Year and Date: 2011-12-06
• [Presentation] Cell-cell contact dependent regulatory role of RFP in integrin beta1 expression (2011)
  • Author(s): 加藤琢哉, 榎本篤, 浅井直也, 村雲芳樹, 高橋雅英
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Cell-cell contact dependent regulatory role of RFP in integrin beta1 expression. (2011)
  • Author(s): 加藤 琢哉
  • Organizer: American Society For Cell Biology
  • Place of Presentation: Colorado Convention Center（コロラド州、アメリカ合衆国）
• [Presentation] Role of RET finger protein in the integrin beta1 expression in cancer cells and its significance in cancer patients (2011)
  • Author(s): 加藤 琢哉
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Orange County Convention Center（フロリダ州、アメリカ合衆国）
• [Presentation] Cell-cell contact dependent regulatory role of RFP in integrin beta1 expression. (2011)
  • Author(s): 加藤 琢哉
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] がん細胞の集団的浸潤の制御機構の解析
  • Author(s): 加藤琢哉
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京（京王プラザホテル）
• [Presentation] Regulatory mechanism of integrin beta1 expression in collectively migrating cancer cells.
  • Author(s): 加藤琢哉
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌（ロイトン札幌）
• [Presentation] Regulatory mechanism of integrin beta1 expression in collectively migrating cancer cells.
  • Author(s): Takuya Kato
  • Organizer: The American Society of Cell Biology, 2012 Annual Meeting.
  • Place of Presentation: サンフランシスコ（アメリカ）
• [Presentation] Regulatory mechanism of integrin beta1 expression in collectively migrating cancer cells.
  • Author(s): Takuya Kato
  • Organizer: 9th AACR-JCA Joint Meeting.
  • Place of Presentation: ハワイ（アメリカ）