Development of diagnostic system of mutations in breast cancer by using primary spheroid cells derived from patients

• Project/Area Number: 26640072
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Gotoh Noriko 金沢大学, がん進展制御研究所, 教授 (10251448)
• Co-Investigator(Kenkyū-buntansha): NAKATA Asuka 金沢大学, がん進展制御研究所, 助教 (70597921) ; SUZUKI Yutaka 東京大学, 新領域創成科学研究科, 教授 (40323646)
• Co-Investigator(Renkei-kenkyūsha): YOSHIDA Ryo 統計数理研究所, モデリング研究系データ同化研究開発センター, 准教授 (70401263) ; TOJO Arinobu 東京大学, 医科学研究所, 教授 (00211681) ; OGAWA Toshihisa 東京大学, 附属病院, 准教授 (80224111) ; INOKUCHI Masashi 金沢大学, 附属病院, 助教 (90401918)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 幹細胞 / 次世代シークエンサー / がん幹細胞 / トリプルネガティブタイプ乳がん / ルミナルタイプ乳がん / MCM10 / 乳がん / スフィア培養 / PDXモデル / RNAシーケンス / エキソームシーケンス

Outline of Final Research Achievements

We performed exome sequence and RNA sequence by using primary cultured cells derived from tumor tissues of breast cancer patients. We analyzed luminal type A, luminal type B and triple negative type breast cancer tissues. We found several novel molecular targets in breast cancer stem-like cells. Functional analysis of these molecules, we identified promising molecular targets of breast cancer stem-like cells.

Research Products

• [Journal Article] Oncogenic fusion gene CD74-NRG1 confers cancer stem cell-like properties in lung cancer through a IGF2 autocrine/paracrine circuit (2016)
  • Author(s): Murayama T, Nakaoku T, Enari T, Nishimura T, Tominaga K, Nakata A, Tojo A, Sugano S, Kohno T, Gotoh N.
  • Journal Title: Cancer Research Volume: 76 Pages: 974-83
  • DOI: 10.1158/0008-5472.can-15-2135
  • NAID: 120005741610
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Elevated β-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs (2015)
  • Author(s): Nakata A, Yoshida R, Yamaguchi R, Yamauchi M, Tamada Y, Fujita A, Shimamura T, Imoto S, Higuchi T, Nomura M, Kimura T, Nokihara H, Higashiyama M, Kondoh K, Nishihara H, Tojo A, Yano S, Miyano S, Gotoh N
  • Journal Title: Scientific Reports Volume: 5 Pages: 13076-13076
  • DOI: 10.1038/srep13076
  • NAID: 130005161518
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Novel Serum 4-microRNA Signature for Lung Cancer Detection (2015)
  • Author(s): Nadal E, Truini A, Nakata A, Lin J, Reddy RM, Chang AC, Ramnath N, Gotoh N, Beer DG, Chen G.
  • Journal Title: Scientific Reports Volume: 5 Pages: 12464-12464
  • DOI: 10.1038/srep12464
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Embryonic microRNA-369 controls metabolic splicing factors and urges cellular reprograming. (2015)
  • Author(s): Masamitsu Konno, Jun Koseki, Koichi Kawamoto, Naohiro Nishida, Hidetoshi Matsui, Dyah Laksmi Dewi, Miyuki Ozaki, Yuko Noguchi, Koshi Mimori, Noriko Gotoh, Nobuhiro Tanuma, Hiroshi Shima, Yuichiro Doki, Masaki Mori , Hideshi Ishii
  • Journal Title: PLoS One Volume: 10(7) Pages: 1-16
  • DOI: 10.1371/journal.pone.0132789
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNAs induce epigenetic reprogramming and suppress malignant phenotypes of human colon cancer cells. (2015)
  • Author(s): Ogawa, H., Wu, X., Kawamoto, K., Nishida, N., Konno, M., Koseki, J., Matsui, H., Noguchi, K., Gotoh, N., Yamamoto, T., Miyata, K., Nishiyama, N., Nagano, H., Yamamoto, H., Obika, S., Kataoka, K., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: PLoS One Volume: 10 Pages: 1-23
  • DOI: 10.1371/journal.pone.0127119
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pyruvate kinase M2, but not M1, allele maintains immature metabolic states of murine embryonic stem cells (2015)
  • Author(s): Konno, M., Ishii, H., Koseki, J., Tanuma, N., Nishida, N., Kawamoto, K., Nishimura, T., Nakata, A., Matsui, H., Noguchi, K., Ozaki, M., Noguchi, Y., Shima, H., Gotoh N., Nagano, H., Doki, Y. and Mori, M.
  • Journal Title: Regenerative Therapy, Volume: 1 Pages: 63-71
  • DOI: 10.1016/j.reth.2015.01.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyclin G2: A novel independent prognostic marker in pancreatic cancer. (2015)
  • Author(s): Hasegawa S, Nagano H, Konno M, Eguchi H, Tomokuni A, Tomimaru Y, Wada H, Hama N, Kawamoto K, Kobayashi S, Marubashi S, Nishida N, Koseki J, Gotoh N, Ohno S, Yabuta N, Nojima H, Mori M, Doki Y, Ishii H.
  • Journal Title: Oncology Letters Volume: 10 Pages: 2986-2990
  • DOI: 10.3892/ol.2015.3667
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell. (2014)
  • Author(s): Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, Kato K, Takenaka K, Iwasaki H, Mizuno S, Goto N, Akashi K.
  • Journal Title: Exp. Hematol Volume: 42 Pages: 955-65
  • DOI: 10.1016/j.exphem.2014.07.267
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial-mesenchymal transition (2014)
  • Author(s): Hamabe, A. Konno, M. Tanuma, N. Shima, H. Tsunekuni, K. Kawamoto, K. Nishida, N. Koseki, J. Mimori, K. Gotoh, N. Yamamoto, H. Doki, Y. Mori, M. Ishii, H.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Pages: 15526-15531
  • DOI: 10.1073/pnas.1407717111
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. (2014)
  • Author(s): Hasegawa S, Eguchi H, Nagano H, Konno M, Tomimaru Y, Wada H, Hama N, Kawamoto K, Kobayashi S, Nishida N, Koseki J, Nishimura T, Gotoh N, Ohno S, Yabuta N, Nojima H, Mori M, Doki Y, Ishii H.
  • Journal Title: B.r J. Cancer Volume: 111 Pages: 1572-1580
  • DOI: 10.1038/bjc.2014.454
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epiregulin enhances tumorigenicity activating ERK/MAPK pathway in glioblastoma. (2014)
  • Author(s): Kohsaka S, Hinohara K, Wang L, Nishimura T, Urushido M, Yachi K, Tsuda M, Tanino M, Kimura T, Nishihara H, Gotoh N, Tanaka S.
  • Journal Title: Neuro. Oncol. Volume: 16 Pages: 960-970
  • Peer Reviewed
• [Journal Article] Fgfr1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation. (2014)
  • Author(s): Ono K
  • Journal Title: PLoS Genet. Volume: 10
  • DOI: 10.1371/journal.pgen.1004118
  • Peer Reviewed
• [Journal Article] Frs2α and Shp2 signal independently of Gab to mediate FGF signaling in lens development. (2014)
  • Author(s): Li H, Tao C, Cai Z, Hertzler-Schaefer K, Collins TN, Wang F, Feng GS, Gotoh N, Zhang X.
  • Journal Title: J. Cell Sci. Volume: 127 Pages: 571-582
  • DOI: 10.1242/jcs.134478
  • Peer Reviewed
• [Presentation] Molecular targets in the signaling and metabolism in cancer stem cells and their niche (2015)
  • Author(s): 後藤典子
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会大会・合同大会ワークショップ「がん治療抵抗性にむけた新しいアプローチ」
  • Place of Presentation: 神戸ポートアイランド、神戸市
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] CD74-NRG1, an oncogenic fusion gene product, leads to insulin-like growth factor 2 autocrine/paracrine circuit and confers cancer stem cell properties (2015)
  • Author(s): 後藤典子
  • Organizer: The 20th Korea-Japan Cancer Research Workshop
  • Place of Presentation: ロイヤルパークホテル ザ 汐留、東京都
  • Year and Date: 2015-11-30
  • Int'l Joint Research / Invited
• [Presentation] 増殖因子によるシグナル制御から得られた耐性克服のための新規分子標的 (2015)
  • Author(s): 後藤典子
  • Organizer: 第56回日本肺癌学会学術集会シンポジウム・「肺癌のトランスレーショナルリサーチ（分子標的薬の耐性克服）」
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2015-11-27
  • Invited
• [Presentation] がん幹細胞―乳がんの癌幹細胞研究と臨床応用への展望 (2015)
  • Author(s): 後藤典子
  • Organizer: 第53回日本癌治療学会・日本癌学会合同シンポジウム：がん治療のゲノム個別化Precision Medicineを目指す多様な視点
  • Place of Presentation: 国立京都国際会館・グランドプリンスホテル京都、京都市
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] Molecular targets in the signaling and metabolism in cancer stem cells and their niche (2015)
  • Author(s): 後藤典子
  • Organizer: 第74回日本癌学会学術総会特別シンポジウム「女性研究者による癌研究」
  • Place of Presentation: 名古屋国際会議場、名古屋市
  • Year and Date: 2015-10-09
  • Invited
• [Presentation] MICAL3 regulates stemness of human breast cancer (2015)
  • Author(s): 後藤典子
  • Organizer: 第13回日本臨床腫瘍学会学術集会シンポジウム「がん幹細胞の分子標的・免疫制御の新展開
  • Place of Presentation: ロイトン札幌・ホテルさっぽろ芸文館、札幌市
  • Year and Date: 2015-07-16
  • Invited
• [Presentation] Maintenance of stemness of breast cancer stem-like cells by FRS2beta, a feedback inhibitor for HER, during mammary tumorigenesis. (2015)
  • Author(s): 後藤典子
  • Organizer: 2015 SNUCRI Cancer Sympotisum
  • Place of Presentation: クムホ ファスン リゾート 光州、韓国
  • Year and Date: 2015-04-03
  • Int'l Joint Research / Invited
• [Presentation] がん幹細胞研究の新展開：多様性と可塑性 (2014)
  • Author(s): 後藤典子
  • Organizer: 第37回日本分子生物学会
  • Place of Presentation: パシフィコ横浜 （横浜）
  • Year and Date: 2014-11-27
  • Invited
• [Presentation] 乳がん幹細胞を標的とした治療戦略 (2014)
  • Author(s): 後藤典子
  • Organizer: 第73回日本癌学会学術総会 腫瘍別シンポジウム
  • Place of Presentation: パシフィコ横浜 （横浜）
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] Insulin-like growth factor regulates breast cancer stem cell properties (2014)
  • Author(s): Gotoh N.
  • Organizer: 2014 SUNCRI Cancer Symposium,
  • Place of Presentation: 華城市（韓国）
  • Year and Date: 2014-04-15
  • Invited