Analysis of cell-context dependent features of adhesion molecules for cancer diagnosis

• Project/Area Number: 25290051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: The University of Tokyo
• Principal Investigator: MURAKAMI Yoshinori 東京大学, 医科学研究所, 教授 (30182108)
• Co-Investigator(Kenkyū-buntansha): 松原 大祐 自治医科大学, 医学部, 准教授 (80415554) ; 後藤 明輝 秋田大学, 医学(系)研究科(研究院), 教授 (90317090) ; 櫻井 美佳 東京大学, 医科学研究所, 助教 (80508359)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000); Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 分子標的薬 / 薬剤耐性 / 肺線がん / EGFR-TKI / 細胞接着 / がん抑制遺伝子 / 耐性 / 細胞接着分子 / 非小細胞肺癌 / 小細胞肺癌 / CADM1 / 肺腺癌 / 増殖因子受容体 / 分子標的

Outline of Final Research Achievements

MET is a receptor of HGF growth factor and is activated by gene amplification and/or overexpression in various cancer to promote cell growth and epithelial to mesenchymal transition. We have demonstrated that a cell adhesion molecule, CADM1, forms a complex with MET on the raft of the cell membrane and suppresses the MET signaling. CADM1 is known to be often inactivated in various cancer cells in their advanced stages. CADM1 could provide a molecular target to suppress oncogenic signaling of cancer cells to malignant growth.

Research Products

• [Int'l Joint Research] Washington University/Johns Hopkins University/University of Texas(米国)
• [Int'l Joint Research] Khon Kaen University(Thailand)
• [Journal Article] NECAB3 Promotes Activation of Hypoxia-inducible factor-1 during Normoxia and Enhances Tumourigenicity of Cancer Cells (2016)
  • Author(s): 1.Nakaoka HJ, Hara T, Yoshino S, Kanamori A, Matsui Y, Shimamura T, Sato H, Murakami Y, Seiki M, Sakamoto T
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 22784-22784
  • DOI: 10.1038/srep22784
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CRTAM determines the CD4+ cytotoxic T lymphocyte lineage. (2016)
  • Author(s): Takeuchi, A., Badr Mel, S., Miyauchi, K., Ishihara, C., Onishi, R., Guo, Z., Sasaki. Y., Ike, H., Takumi, A., Tsuji, NM., Murakami, Y., Katakai, T., Kubo, M. and Saito, T.
  • Journal Title: J. Exp. Med. Volume: 213 Issue: 1 Pages: 123-138
  • DOI: 10.1084/jem.20150519
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Frequent copy gain of the MET gene in hypopharyngeal and larynxeal cancer in the Japanese population (2015)
  • Author(s): Akashi K, Ebihara Y, Omura G, Saito Y, Yoshida M, Ando M, Asakage T, Yamasoba T, Murakami Y
  • Journal Title: Journal of Cancer Therapy Volume: 6 Issue: 12 Pages: 1093-1102
  • DOI: 10.4236/jct.2015.612119
  • Peer Reviewed / Open Access
• [Journal Article] A measles virus selectively blind to signaling lymphocytic activation molecule shows anti-tumor activity against lung cancer cells. (2015)
  • Author(s): Fujiyuki T, Yoneda M, Amagai Y, Obayashi K, Ikeda F, Shoji K, Murakami Y, Sato H, Kai C.
  • Journal Title: Oncotarget, Volume: 6 Issue: 28 Pages: 24895-24903
  • DOI: 10.18632/oncotarget.4366
  • Peer Reviewed / Open Access
• [Journal Article] Promoter Methylation of the CADM1 and 4.1B Genes Occurs Independently of the EGFR or the KRAS2 Mutation in Non-Small Cell Lung Cancer. (2015)
  • Author(s): Hiroyuki Kogai, Shinji Kikuchi, Takashi Obana, Yumi Tsuboi, Tomoko Maruyama, Mika Sakurai-Yageta, Hisao Asamura, Yae Kanai, Yoshinori Murakami.
  • Journal Title: Journal of Cancer Therapy. Volume: 6 Issue: 03 Pages: 273-285
  • DOI: 10.4236/jct.2015.63030
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic Regulation of a Cell Adhesion Protein Complex Including CADM1 by Combinatorial Analysis of FRAP with Exponential Curve-fitting (2015)
  • Author(s): Sakurai-Yageta, M., Maruyama,T., Suzuki, T., Ichikawa, K., and Murakami, Y.
  • Journal Title: PLoS ONE Volume: 10 Issue: 3 Pages: 0116637-0116637
  • DOI: 10.1371/journal.pone.0116637
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical analysis of the expression of E-cadherin and ZEB1 in non-small cell lung cancer. (2014)
  • Author(s): Matsubara D, Kishaba Y, Yoshimoto T, Sakuma Y, Sakatani T, Tamura T, Endo S, Sugiyama Y, Murakami Y, Niki T
  • Journal Title: Pathology International Volume: 64 Issue: 11 Pages: 560-568
  • DOI: 10.1111/pin.12214
  • Peer Reviewed / Open Access
• [Journal Article] High incidence of null-type mutations of the TP53 gene in Japanese patients with head and neck squamous cell carcinoma. (2014)
  • Author(s): Ebihara Y, Iwai M, Akashi K, Ito T, Omura G, Saito Y, Yoshida M, Ando M, Asakage T, Yamasoba T, Murakami Y.
  • Journal Title: Journal of Cancer Therapy Volume: 5 Pages: 664-671
  • Open Access / Acknowledgement Compliant
• [Journal Article] Detection of lung tumors in mice using a 1-Tesla compact magnetic resonance imaging system. (2014)
  • Author(s): Wang F, Akashi K, Murakami Y, Inoue Y, Furuta T, Yamada H, Ohtomo K, Kiryu S.
  • Journal Title: PLoS One, Volume: 9 Issue: 4 Pages: e94945-e94945
  • DOI: 10.1371/journal.pone.0094945
  • Peer Reviewed / Open Access
• [Journal Article] Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition. (2014)
  • Author(s): Ibrahim R, Matsubara D, Osman W, Morikawa T, Goto A, Morita S, Ishikawa S, Aburatani H, Takai D, Nakajima J, Fukayama M, Niki T, Murakami Y
  • Journal Title: Hum Pathol. Volume: 45 Issue: 7 Pages: 1397-405
  • DOI: 10.1016/j.humpath.2014.02.013
  • Peer Reviewed / Open Access
• [Journal Article] CRTAM controls residency of gut CD4+CD8+T cells in the steady state and maintenance of gut CD4 TH17 during parasitic infection. (2014)
  • Author(s): Cortez VS, Cervantes-Barragan L, Song C, Gilfillan S, McDonald KG, Edelson BT, Murakami Y, Newberry RD, Sibley LD, Colonna M.
  • Journal Title: J Exp. Med. Volume: 211 Issue: 4 Pages: 623-633
  • DOI: 10.1084/jem.20130904
  • Peer Reviewed / Open Access
• [Journal Article] Trans-homophilic interaction of CADM1 activates PI3K by forming a complex with MAGuK-family proteins MPP3 and Dlg. (2014)
  • Author(s): Murakami, S., Sakurai-Yageta, M. (equal contribution), Maruyama, T., Murakami, Y.
  • Journal Title: PloS One Volume: 9(2) Issue: 2 Pages: e82894-e82894
  • DOI: 10.1371/journal.pone.0082894
  • Peer Reviewed / Open Access
• [Journal Article] Adhesion molecule CADM1 contributes to gap junctional communication among pancreatic islet α-cells and prevents their excessive secretion of glucagon (2014)
  • Author(s): Ito A, Ichiyanagi N, Ikeda Y, Hagiyama M, Inoue T, Kimura KB, Sakurai MA, Hamaguchi K, Murakami Y.
  • Journal Title: Islet Volume: in press
  • Peer Reviewed
• [Journal Article] CRTAM controls residency of gut CD4+CD8+T cells in the steady state and maintenance of gut CD4 TH17 during parasitic infection. (2014)
  • Author(s): Cortez VS, Cervantes-Barragan L, Song C, Gilfillan S, McDonald KG, Edelson BT, Murakami Y, Newberry RD, Sibley LD, Colonna M.
  • Journal Title: Journal of Experimental Medicine Volume: in press
  • Peer Reviewed
• [Journal Article] Detection of lung tumors in mice using a 1-Tesla compact magnetic resonance imaging system. (2014)
  • Author(s): Wang F, Akashi K, Murakami Y, Inoue Y, Furuta T, Yamada H, Ohtomo K, Kiryu S.
  • Journal Title: PLoS One Volume: in press
  • Peer Reviewed
• [Journal Article] Genomic and transcriptional alterations of cholangiocarcinoma. (2014)
  • Author(s): Ito A, Sakurai M, Goto A, Pairojkul C, Yongvanit P, Murakami Y.
  • Journal Title: J Hepato-Biliary and Pancreatic Science Volume: in press
  • Peer Reviewed
• [Journal Article] HPV-associated lung cancers: an international pooled analysis. (2014)
  • Author(s): Ragin C, Obikoya-Malomo M, Kim S, Chen Z, Flores-Obando R, Gibbs D, Koriyama C, Aguayo F, Koshiol J, Caporaso NE, Carpagnano GE, Ciotti M, Dosaka-Akita H, Fukayama M, Goto A et al
  • Journal Title: Carcinogenesis Volume: in press
  • Peer Reviewed
• [Journal Article] Preface: international collaboration to control cholangiocarcinoma. (2014)
  • Author(s): Murakami Y, Yamamoto M.
  • Journal Title: J Hepato-Biliary and Pancreatic Science Volume: in press
  • Peer Reviewed
• [Journal Article] Lung cancer with loss of BRG1?BRM,shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features. (2013)
  • Author(s): Matsubara D, Murakami Y, Niki T et al.
  • Journal Title: Cancer Sci Volume: 104 Issue: 2 Pages: 266-273
  • DOI: 10.1111/cas.12065
  • Peer Reviewed
• [Journal Article] High-grade Lung Adenocarcinoma With Fetal Lung-like Morphology: Clinicopathologic, Immunohistochemical, and Molecular Analyses of 17 Cases (2013)
  • Author(s): Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H.
  • Journal Title: Am J Surg Pathol Volume: 37(6) Issue: 6 Pages: 924-932
  • DOI: 10.1097/pas.0b013e31827e1e83
  • Peer Reviewed
• [Journal Article] Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates eytokinesis, and its expression correlates with the prognosis of renal cell earcinoma. (2013)
  • Author(s): Shoji K, Mimura I, Murayama T, Wada T, Kume H, Goto A, Ohse T, Tanaka T, Inagi R, van der Hoorn FA, Manabe I, Homma Y, Fukayama M, Sakurai T, Hasegawa T, Aburatani H, Kodama T, Nangaku M.
  • Journal Title: American Journal of Pathology Volume: 182 Issue: 6 Pages: 2191-2203
  • DOI: 10.1016/j.ajpath.2013.02.024
  • Peer Reviewed
• [Presentation] Mathematical analysis of the dynamics of CADM1 and its role in the MET-driven resistance against EGFR-TKI in lung adenocarcinoma. (2016)
  • Author(s): Ito T, Sakurai-Yageta M, Tsuchiya T, Kawasaki S, Ohba M, Ichikawa K, Suzuki T, Murakami Y.
  • Organizer: The First JSPS Core-to-Core Seminar: Establishing Research Network of Mathematical Oncology
  • Place of Presentation: 大和高原ボスコヴィラ(奈良県奈良市）
  • Year and Date: 2016-03-08
  • Int'l Joint Research
• [Presentation] Dual roles of a Cell Adhsion Molecule CADM1 in Oncogenesis. (2016)
  • Author(s): Ito T, Tsuchiya T, Kumagai Y, Tsuboi Y, Sakurai-Yageta M, Oba M and Murakami Y.
  • Organizer: The 10th AACR-JCA Joint Symposium of Cancer Research
  • Place of Presentation: Maui, Hawai, USA
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Roles of a cell adhesion molecule CADM1 in apoptosis induction, invasion and metastasis. (2015)
  • Author(s): Murakami Y, Ito T, Kogai H, Sakurai-Yageta M, Kumagai Y, Matsubara D.
  • Organizer: The 74th Annual Meeting of Japanese Cancer Association. Symposium
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] Roles of a cell adhesion molecule CADM1 in apoptosis induction, invasion and metastasis. (2015)
  • Author(s): Murakami Y, Matsuda K, Kubo M.
  • Organizer: 東京大学ゲノム医科学研究機構キックオフ・シンポジウム
  • Place of Presentation: 伊藤国際ホール（東京都文京区）
  • Year and Date: 2015-08-29
  • Invited
• [Presentation] Analysis of the role of CADM1 in suppression of lung cancer using Cadm1-deficient mice. (2015)
  • Author(s): Ito T, Nagata M, Kawai T, Maruyama T, Sakurai-Yageta M, Ito A, Goto A, Matsubara D, Murakami Y.
  • Organizer: AACR Annual Meeting
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 2015-04-16
  • Int'l Joint Research
• [Presentation] Genomic and transcriptional alterations of cholangiocarcinoma. (2015)
  • Author(s): Ito T, Sakurai-Yageta M, Goto A, Murakami Y.
  • Organizer: The 1st International Symposium for Biomarkers of Cholangiocarcinoma
  • Place of Presentation: 東京都
  • Year and Date: 2015-01-24
  • Invited
• [Presentation] Involvement of CADM1 in apoptosis induction of detached epithelial cells as a new type of dependence receptor. (2014)
  • Author(s): Kogai H, Sakurai-Yageta M, Delloye-Bourgeois C, Tauszig-Delamasure S, Mehlen P, Murakami Y.
  • Organizer: 4th France-Japan Cancer Workshop、
  • Place of Presentation: 京都市
  • Year and Date: 2014-11-18 – 2014-11-21
  • Invited
• [Presentation] Involvement of a cell adhesion molecule CADM1 in oncogenesis. (2014)
  • Author(s): Murakami Y.
  • Organizer: The 2nd International Alliance Research Internship Program Symposium of the University of Lyon.
  • Place of Presentation: フランス リヨン市
  • Year and Date: 2014-11-03 – 2014-11-04
  • Invited
• [Presentation] Involvement of CADM1 in apoptosis induction of detached epithelial cells as a new type of dependence receptor. (2014)
  • Author(s): Kogai H, Sakurai-Yageta M, Tauszig-Delamasure S, Mehlen P, Murakami Y.
  • Organizer: The 20th International Charles Heidelberger Symposium on Cancer Research、
  • Place of Presentation: チリ アリカ市
  • Year and Date: 2014-10-08 – 2014-10-11
  • Invited
• [Presentation] Roles of a cell adhesion molecule CADM1 in epithelial integrity and malignant phenotype of cancer cells. (2014)
  • Author(s): Murakami Y.
  • Organizer: The 73rd Annual Meeting of Japanese Cancer Association
  • Place of Presentation: 横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] Context dependent features of a cell adhesion molecule CADM1 in human oncogenesis. (2014)
  • Author(s): Ito T, Kogai H, Murakami S, Sakurai-Yageta M, Matsubara D, Murakami D. .
  • Organizer: The 21st East Asia Joint Conference
  • Place of Presentation: 韓国 京城市
  • Year and Date: 2014-07-15 – 2014-07-18
  • Invited
• [Presentation] A cell adhesion molecule, CADM1, as a new type of dependence receptor. (2014)
  • Author(s): Kogai H, Sakurai-Yageta M, Delloye-Bourgeois C, Tauszig-Delamasure S, Mehlen P, Murakami Y.
  • Organizer: The 5th Dependence Receptor International Meeting.
  • Place of Presentation: Les Menuires, France
  • Invited
• [Presentation] Copy Number Variation (CNV) 部位におけるがん組織の体細胞変異の解析 (2013)
  • Author(s): 村上善則、平 郁、明石健、金谷淳志、伊東剛、齋藤光江、江見充
  • Organizer: 第58回日本人類遺伝学会年会、シンポジウム 1 「がんゲノム研究の最前線」
  • Place of Presentation: 仙台市
  • Invited
• [Presentation] Dual roles of a cell adhesion molecule, CADM1, in human oncogenesis. Pathogenesis, Gene Regulation and Signal Transduction. (2013)
  • Author(s): Ito T, Sakurai M, Matsubara D, Murakami Y.
  • Organizer: The 9th China-Japan Joint Laboratory Workshop.
  • Place of Presentation: Beijing, China
  • Invited
• [Presentation] Roles of a cell adhesion molecule CADM1 in epithelial integrity, invasion and metastasis. Symposium 9 “Research on Tumor Invasion and Metastasis toward Clinical Application. (2013)
  • Author(s): Murakami Y.
  • Organizer: The 72th Annual Meeting of Japanese Cancer Association.
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] The role of CADM1 on regeneration of intestinal epithelia in ulcerative colitis (2013)
  • Author(s): Ikeda Y, Tsuboi Y, Matsubara D, Murakami Y
  • Organizer: The 72th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] Lipoma preferred partner regulates N-cadherin shedding by MMP15 during lung adenocarcinoma metastasis (2013)
  • Author(s): Kuriyama S, Yano S, Goto A, Tanaka M
  • Organizer: The 72th Annual Meeting of Japanese Cancer Association
  • Place of Presentation: 横浜市
  • Invited
• [Remarks] 東京大学医科学研究所人癌病因遺伝子分野
  • URL: http://www.ims.u-tokyo.ac.jp/hitogan/index.html
• [Remarks] 東京大学医科学研究所人癌病因遺伝子分野ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/hitogan/sub10.html