Physiological and pathological analyses of cell adhesion molecules towards the development of diagnostic markers of human cancer

• Project/Area Number: 22300336
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnosis
• 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): ITO Akihiko 近畿大学, 医学部, 教授 (80273647) ; SAKURAI Mika 東京大学, 医科学研究所, 助教 (80508359) ; GOTO Akiteru 秋田大学, 大学院・医学系研究科, 教授 (90317090) ; MATSUBARA Daisuke 東京大学, 医科学研究所, 講師 (80415554)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2012: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: がんの個性診断 / 細胞接着分子 / CADM1 / 非小細胞肺癌 / 小細胞肺癌 / MET / 分子標的薬 / miRNA / 糖鎖修飾 / 肺がん / 腎細胞がん / 乳がん / ATL / 増殖因子受容体

Research Abstract

Physiological and pathological roles of cell adhesion molecules in cancer development and progression were analyzed to establish novel molecular markers of human cancer. We found that a splicing variant of a cell adhesion molecule CADM1 was expressed exclusively in small cell lung cancer (SCLC), providing a candidate diagnostic marker of SCLC. We also found that CADM1 could cross-talk with the MET signaling and may play a role in acquired resistance of lung adenocarcinoma against EGFR-TKItreatment.

Research Products

• [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] Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad. (2012)
  • Author(s): Matsubara D, Murakami Y, Niki T et al.
  • Journal Title: J Thorac Oncol Volume: 7 Issue: 12 Pages: 1872-1876
  • DOI: 10.1097/jto.0b013e3182721ed1
  • Peer Reviewed
• [Journal Article] Involvement of miR-214 and miR-375 in malign.ant features of non-small-cell lung cancer by down-regulating CADM1. (2012)
  • Author(s): Ishimura M, Sakurai-Yageta M,Maruyama T, Ando T, Fukayama M,Goto A, Murakami Y.
  • Journal Title: J Cancer Therapy Volume: 3 Issue: 04 Pages: 379-387
  • DOI: 10.4236/jct.2012.324050
  • Peer Reviewed
• [Journal Article] Novel application for pseudopodia proteomics using excimer laser ablation and two-dimensional difference gel electrophoresis. (2012)
  • Author(s): Ito A, Murakami Y, Kondo T et al.
  • Journal Title: Lab Invest Volume: 92 Issue: 9 Pages: 1374-1385
  • DOI: 10.1038/labinvest.2012.98
  • Peer Reviewed
• [Journal Article] Expression of a splicing variant of the CADM1 specific to small cell lung cancer (2012)
  • Author(s): Kikuchi S, Iwai M, Sakurai-Yageta M, Tsuboi Y, Ito T, Maruyama T, Tsuda H, Kanai Y, 0nizuka M, Sato Y, Murakami Y
  • Journal Title: Cancer Science Volume: 103 Issue: 6 Pages: 1051-1057
  • DOI: 10.1111/j.1349-7006.2012.02277.x
  • Peer Reviewed
• [Journal Article] Notch2 and Six1 are up-regulated during progression of early-stage lung adenocarcinoma and define its unfavorable subset at advanced stages. (2012)
  • Author(s): Mimae T, Murakami Y, Ito A et al.
  • Journal Title: Clinical Cancer Research Volume: 18 Issue: 4 Pages: 945-948
  • DOI: 10.1158/1078-0432.ccr-11-1946
  • Peer Reviewed
• [Journal Article] Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex (2012)
  • Author(s): 長柄雄介
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 417 Issue: 1 Pages: 462-467
  • DOI: 10.1016/j.bbrc.2011.11.140
  • Peer Reviewed
• [Journal Article] Aberrant expression of tumor suppressors, CADM1 and 4. IB, in invasive lesions of primary breast cancer (2012)
  • Author(s): Takahashl Y, Iwai M, Kawai T, Arakawa A, Ito T, Sakurai-Yageta M, Ito A, Goto A, Saito M, Kasumi F, Murakami Y
  • Journal Title: Breast Cancer Volume: (掲載確定) Issue: 3 Pages: 242-252
  • DOI: 10.1007/s12282-011-0272-7
  • Peer Reviewed
• [Journal Article] Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma (2012)
  • Author(s): Nagata M, et al.
  • Journal Title: Int.J Cancer Volume: 130 Issue: 6 Pages: 1329-37
  • DOI: 10.1002/ijc.26160
  • Peer Reviewed
• [Journal Article] Genome structure-based screening identifiedepigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer. (2012)
  • Author(s): Watanabe K, Goto A, Takai D.
  • Journal Title: Int J Cancer. Volume: 130 Issue: 11 Pages: 2580-2590
  • DOI: 10.1002/ijc.26254
  • Peer Reviewed
• [Journal Article] B cells regulate antibody responses through the medullary remodeling of inflamed lymph nodes. (2012)
  • Author(s): Abe J, Goto A, Matsushima K et al.
  • Journal Title: Int Immunol Volume: 24 Pages: 17-27
• [Journal Article] Involvement of miR-214 and miR-375 in malign.ant features of non-small-cell lung cancer by down-regulating CADM1. (2012)
  • Author(s): Ishimura M, Sakurai-Yageta M, Maruyama T, Ando T, Fukayama M, Goto A, Murakami Y.
  • Journal Title: J Cancer Therap Volume: 3 Pages: 379-387
  • Peer Reviewed
• [Journal Article] Expression of a splicing variant of the CADM1 specific to small cell lung cancer (2012)
  • Author(s): Kikuchi S, Sakurai M, Murakami Y, et al. (11著中、最終著者)
  • Journal Title: Cancer Science Volume: (in press)
  • Peer Reviewed
• [Journal Article] Aberrant expression of tumor suppressors, CADM1 and 4.1B, in invasive lesions of primary breast cancer (2012)
  • Author(s): Takahashi Y, Sakurai M, Murakami Y, et al.(11著者中、最終著者)
  • Journal Title: Breat Cancer Volume: (in press)
  • NAID: 10031170651
  • Peer Reviewed
• [Journal Article] Notch2 and Six1 are up-regulated during progression of early-stage lung adenocarcinoma and define its unfavorable subset at advanced stages (2012)
  • Author(s): Mimae T, Murakami Y, Ito A, et al.(8著者中,第2最終著者)
  • Journal Title: Clinical Cancer Research Volume: (in press)
  • Peer Reviewed
• [Journal Article] A Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by A disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by gamma-secretase (2012)
  • Author(s): Nagara Y, Murakami Y, Ito A, et al.(9著者中,第7著者)
  • Journal Title: Biochemical Biophysical Research Communication Volume: (in press)
  • Peer Reviewed
• [Journal Article] Adhesion molecule CADM1 contributes to gap junctional communication among pancreatic islet beta cells and prevents their excessive secretion of glucagon (2012)
  • Author(s): Ito A, Murakami Y, et al.(9著者中、最終著者)
  • Journal Title: Islet Volume: (in press)
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of the CADM1 gene by retinoic acid during the neural differentiation of murine embryonal carcinoma P19 cells. (2011)
  • Author(s): Ito T, Sakurai-Yageta M, Murakami Y et al.
  • Journal Title: Genes to Cells Volume: 16 Pages: 791-802
• [Journal Article] Steroid Receptor Expression in Thymomas and Thymic Carcinomas (2011)
  • Author(s): Mimae T, Murakami Y, Tsuda H.
  • Journal Title: Cancer Volume: 117 Issue: 19 Pages: 4396-4405
  • DOI: 10.1002/cncr.26061
• [Journal Article] Enhanced nerve-mast cell interaction by a neuronal short isoform of cell adhesion molecule-1 (2011)
  • Author(s): Hagiyama M, Furuno T, Hosokawa Y, Iino I, Ito T, Inoue T, Nakanishi M, Murakami Y, Ito A
  • Journal Title: The Journal of Immunology Volume: 186 Issue: 10 Pages: 5983-5992
  • DOI: 10.4049/jimmunol.1002244
  • Peer Reviewed
• [Journal Article] Non-contact estimation of intercellular breaking force using a femtosecond laser impulse quantified by atomic force microscopy. Proc. (2011)
  • Author(s): Hosokawa Y, Murakami Y, Ito A.
  • Journal Title: Natl. Acad. Sci. USA Volume: 108 Issue: 5 Pages: 1777-1872
  • DOI: 10.1073/pnas.1006847108
• [Journal Article] CpG island methylation of microRNAs is associated with tumor size and recurrence of non-small-cell lung cancer. (2011)
  • Author(s): Kitano K, Goto A, Takai D et al.
  • Journal Title: Cancer Sci. Volume: 102 Pages: 2126-31
  • NAID: 10030245653
• [Journal Article] Human papillomavirus infection in lung and esophagealcancers: analysis of 485 Asian cases. (2011)
  • Author(s): Goto A, Fukayama M et al.
  • Journal Title: J Med Virol. Volume: 83 Issue: 8 Pages: 1383-1390
  • DOI: 10.1002/jmv.22150
  • Peer Reviewed
• [Journal Article] Multicystic mesothelioma of the pericardium. (2011)
  • Author(s): Morita S, Goto A, Fukayama M et al.
  • Journal Title: Pathol Int. Volume: 61 Pages: 319-21
  • NAID: 10031185089
• [Journal Article] Pleural cavity angiosarcoma arising in chronic expanding hematoma after pneumonectomy. (2011)
  • Author(s): Miyazaki H, Goto A, Fukayama M et al.
  • Journal Title: Hum Pathol Volume: 42 Issue: 10 Pages: 1576-1579
  • DOI: 10.1016/j.humpath.2010.06.019
• [Journal Article] Transcriptional regulation of the CADM1 gene by retinoic acid during the neural differentiation of murine embryonal carcinoma P19 cells (2011)
  • Author(s): Ito T, Ito A, Sakurai M, Murakami Y, et al. (8著者中、最終著者)
  • Journal Title: Genes to Cells Volume: 16 Pages: 791-802
  • Peer Reviewed
• [Journal Article] Enhanced Nerve-Mast Cell Interaction by a Neuronal Short Isoform of Cell Adhesion Molecule-1, CADM1 (2011)
  • Author(s): Hagiyama M, Murakami Y, Ito A, et al.(9著者中、第2最終著者)
  • Journal Title: Journal of Immunology Volume: 186 Pages: 5983-5992
  • Peer Reviewed
• [Journal Article] Non-contact estimation of intercellular breaking force using a femtosecond laser impulse quantified by atomic force microscopy (2011)
  • Author(s): Hosokawa Y, Murakami Y, Ito A, et al.(6著者中、第2最終著者)
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 1777-1782
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of the CADM1 gene by retinoic acid during the neural differentiation of murine embryonal carcinoma P19 cells. (2011)
  • Author(s): Ito T, Sakurai-Yageta M, Murakami Y, et al.(最終著者)
  • Journal Title: Genes to Cells Volume: (in press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Aberrant expression of tumor suppressors, CADM1 and 4.1B, in invasive lesions of primary breast cancer. (2011)
  • Author(s): Takahashi Y, Sakurai M, Murakami Y, et al.(最終著者)
  • Journal Title: Breast Cancer Volume: (in press)(掲載確定)
  • NAID: 10031170651
  • Peer Reviewed
• [Journal Article] Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma. (2011)
  • Author(s): Nagata M, Sakurai M, Murakami Y, et al.(最終著者)
  • Journal Title: International Journal of Cancer Volume: (in press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Enhanced Nerve-Mast Cell Interaction by a Neuronal Short Isoform of Cell Adhesion Molecule-1, CADM1. (2011)
  • Author(s): Hagiyama M, Murakami Y, Ito A, et al.(第2最終著者)
  • Journal Title: Journal of Immunology Volume: (in press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Non-contact estimation of intercellular breaking force using a femtosecond laser impulse quantified by atomic force microscopy. (2011)
  • Author(s): Hosokawa Y, Murakami Y, Ito A, et al.(第2最終著者)
  • Journal Title: Proceedings of the National Academy of Science Volume: 108 Pages: 1777-1782
  • Peer Reviewed
• [Journal Article] Steroid Receptor Expression in Thymomas and Thymic Carcinomas. (2011)
  • Author(s): Mimae T, Murakami Y, Tsuda H, et al.(10人中第6著者)
  • Journal Title: Cancer Volume: (in press)(掲載確定)
  • Peer Reviewed
• [Journal Article] CADM1 interacts with Tiam1 and promotes invasivephenotype of human T-cell leukemia virus type I (HTLV-I) transformed cells and adult T-cell leukemia (ATL) cells. (2010)
  • Author(s): Masuda M, Murakami Y et al.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Issue: 20 Pages: 15511-15522
  • DOI: 10.1074/jbc.m109.076653
• [Journal Article] CADM1 interacts with Tiaml and promotes invasive phenotype of human T-cell leukemia virus type I (HTLV-I) transformed cells and adult T-cell leukemia (ATL) cells. (2010)
  • Author(s): Masuda M, Ito A, Murakami Y, et al.(最終著者)
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 15511-15522
  • Peer Reviewed
• [Journal Article] Adhesion molecule CADM1 contributes to gap junctional communication among pancreatic islet beta cells and prevents their excessive secretion of glucagon.
  • Author(s): Ito A, Murakami Y et al
  • Journal Title: Islet. in press.
• [Presentation] Roles of a cell adhesion molecule CADM1 in malignantprogression of non-small cell lung cancer. (2013)
  • Author(s): Yoshinori Murakami.
  • Organizer: The 3rdJoint Symposium of the Max-Planck Society and University of Tokyo Graduate School of Medicine.
  • Place of Presentation: 東京、日本
  • Year and Date: 2013-03-08
• [Presentation] Roles of a cell adhesion molecule CADM1 in malignant progression of non-small cell lung cancer. (2013)
  • Author(s): 1. Takeshi Ito, Hideki Kuwano, Mika Sakurai-Yageta, Yumi Tsuboi, Daisuke Matsubara and Yoshinori Murakami.
  • Organizer: The 19th International Charles Heidelberger Symposium on Cancer Research.
  • Place of Presentation: Kagoshima, Japan
  • Invited
• [Presentation] Towards the control of cholangiocarcinoma by international collaboration between Thailand and Japan. (2013)
  • Author(s): 2. Yoshinori Murakami, Masanao Miwa, Hideo Tanaka, Masakazu Yamamoto and Puangrat Yongvanit.
  • Organizer: The International Symposium on Cholangiocarcinoma, Tokyo
  • Place of Presentation: Tokyo, Japan
  • Invited
• [Presentation] Roles of a cell adhesion molecule CADM1 in malignant progression of non-small cell lung cancer. (2012)
  • Author(s): Yoshinori Murakami.
  • Organizer: The 2nd France-Japan Cancer Workshop
  • Place of Presentation: Naruto, Japan
  • Invited
• [Presentation] Dual roles of a cell adhesion molecule, CADM1, in human oncogenesis. (2012)
  • Author(s): Yoshinori Murakami.
  • Organizer: The 18th International Charles Heidelberger Symposium on Cancer Research.
  • Place of Presentation: Ulm, Germany
  • Invited
• [Presentation] Dual roles of a cell adhesion molecule, CADM1, in human lung oncogenesis based on the molecular pathological analyses. (2012)
  • Author(s): Yoshinori Murakami, Mika Sakurai, Takeshi Ito, Hideki Kuwano, Daisuke Matsubara, Akiteru Goto.
  • Organizer: 第７１回日本癌学会
  • Place of Presentation: 札幌、日本
• [Presentation] Dual roles of a cell adhesion molecule, CADM1, in human oncogenesis (2011)
  • Author(s): Murakami Y.
  • Organizer: The 18th East Asia Joint Symposium-Life Science Today in East Asia
  • Place of Presentation: 中国・上海市(招待講演)
  • Year and Date: 2011-12-09
• [Presentation] Dual roles of a cell adhesion molecule, CADM1, in human oncogenesis (2011)
  • Author(s): Murakami Y.
  • Organizer: The 1st France-Japan Cancer Workshop
  • Place of Presentation: フランス・モンペリエ市(招待講演)
  • Year and Date: 2011-11-23
• [Presentation] Copy Number Variation (CNV)の網羅的検索による癌のゲノム異常の解析 (2011)
  • Author(s): 村上善則、齊藤光江、江見充
  • Organizer: 日本人類遺伝学会第56回大会シンポジウム
  • Place of Presentation: 千葉市
  • Year and Date: 2011-11-11
• [Presentation] Dual roles of a cell adhesion molecule, CADM1, in human oncogenesis (2011)
  • Author(s): Murakami Y, Skurai M, et al.(8著者中第1著者)
  • Organizer: The 3rd CREST-SBM International Conference : Mathematical Methods in Cancer Cell Biology
  • Place of Presentation: 広島市
  • Year and Date: 2011-06-09
• [Presentation] Dual roles of a cell adhesion molecule, CADM1, in human oncogenesis (2011)
  • Author(s): Murakami Y.
  • Organizer: The 17th Charles Heidelberger International Symposium
  • Place of Presentation: 中国・西安市(招待講演)
  • Year and Date: 2011-06-06
• [Presentation] 膜タンパク質CADM1による細胞の接着と浸潤の制御。第100回日本病理学会総会ワークショップ (2011)
  • Author(s): 村上善則、伊藤彰彦、後藤明輝
  • Organizer: 第100回日本病理学会総会ワークショップ
  • Place of Presentation: 横浜市
  • Year and Date: 2011-04-29
• [Presentation] Spontaneous development of lung adenocarcinoma in the Cadm1 gene-deficient mice (2010)
  • Author(s): Nagata M, Sakurai M, Murakami Y, et al.(最終著者)
  • Organizer: The 16^<th> Charles Heidelberger International Symposium on Cancer Research
  • Place of Presentation: ポルトガル、コインブラ市
  • Year and Date: 2010-09-27
• [Presentation] A cell adhesion moleclue, CADM1, interacts with Tiam1 and promotes invasive phenotype of human adult T-cell leukemia cells (2010)
  • Author(s): Murakami Y, Masuda M, et al.(第一著者)
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Book] がん生物学イラストレイテッド (2011)
  • Author(s): 渋谷正史、湯浅保仁編
  • Publisher: 羊土社
• [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]
  • URL: http://www.ims.u-tokyo.ac.jp/hitogan/index.html
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/hitogan/index.html
• [Patent(Industrial Property Rights)] がんの診断、処置および/または予防、および/または浸潤・転移の抑制のための方法、システムおよび組成物ならびに関連するスクリーニング方法 (2012)
  • Inventor(s): 村上善則、増田万里・国立大学法人東京大学
  • Industrial Property Rights Holder: 村上善則、増田万里・国立大学法人東京大学
  • Acquisition Date: 2012-11-16
  • Overseas
• [Patent(Industrial Property Rights)] 小細胞肺癌がんの診断のための方法、システムおよび組成物ならびに関連するスクリーニング方法 (2012)
  • Inventor(s): 村上善則・国立大学法人東京大学
  • Industrial Property Rights Holder: 村上善則・国立大学法人東京大学
  • Acquisition Date: 2012-11-16
  • Overseas