Molecular mechanism for collective invasion of cancer cell groups

2012 Fiscal Year Final Research Report

• 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
• Keywords: collective invasion

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 Pages: 1144
  • DOI: DOI:10.1038/srep01144
  • 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
  • Peer Reviewed
• [Journal Article] Involvement of Girdin in the determination of cell polarity during cell migration (2012)
  • Author(s): Ohara K, Enomoto A, Kato T, Hashimoto T, Isotani-Sakakibara M, Asai N, Ishida-Takagishi M, Weng L, Nakayama M, Watanabe T, Kato K, Kaibuchi K, Murakumo Y, Hirooka Y, Goto H, Takahashi M
  • Journal Title: PLoS One Volume: 7(5) Pages: e36681
  • DOI: 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, Asai N, Ushida K, Watanabe T, Hashimoto T, Kato T, Weng L, Matsumoto S, Asai M, Murakumo Y, Kaibuchi K, Kikuchi A, Takahashi M
  • Journal Title: Nat Commun Volume: 29 Pages: 3:859
  • DOI: 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] 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
• [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