Functional analysis of key molecule of breast cancer stem cells

• Project/Area Number: 23790357
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: HINOHARA Kunihiko 東京大学, 医科学研究所, 特任助教 (50549467)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: breast cancer / cancer stem cells / HRG / ErbB / PI3K / IGF / IGF2 / sphere / growth factor / ID3 / がん幹細胞 / 増殖因子 / 乳がん / HER / NF-κB / breast cancer stem cells

Research Abstract

We identified HRG/ErbB signaling as a key molecular mechanism on regulating breast cancer stem cell properties. ErbB signaling maintains breast cancer stem cell properties via PI3K/NF-kappaB pathway, suggesting that crosstalk between growth factor signaling and inflammatory response pathway is important for such regulation. Moreover, IGF2 signaling is required for maintenance of the breast cancer stem cell properties as a downstream mediator of PI3K signaling. Also, HRG signature and IGF signature identified by microarray analysis is strongly associated with both breast cancer grade and prognosis such as metastasis or relapse. These observations suggest that these growth factor signaling have important roles on malignant progression of breast cancer through maintenance of breast cancer stem cell properties.

Research Products

• [Journal Article] Epiregulin enhances tumorigenicity by activating the ERK/MAPK pathway in glioblastoma (2014)
  • Author(s): Kohsaka S, Hinohar a 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: (Epub ahead of print)
• [Journal Article] Epiregulin enhances tumorigenicity by activating the 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: -
  • Peer Reviewed
• [Journal Article] The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein (2013)
  • Author(s): Kano Y, Tsuchiya K, Zheng X, Horita N, Fukushima K, Hibiya S, Yamauchi Y, Nishimura T, Hinohar a K, Gotoh N, Suzuki S, Okamoto R, Nakamura T, Watanabe M
  • Journal Title: Biochem Biophys Res Commun Volume: 432(1) Pages: 175-181
• [Journal Article] Effect of in vivo administration of reprogramming factors in the mouse liver (2013)
  • Author(s): Tomokuni A, Eguchi H, Hoshino H, Dewi DL, Nishikawa S, Kano Y, Miyoshi N, Tojo A, Kobayashi S, Gotoh N, Hinohar a K, Fusaki N, Saito T, Suemizu H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Doki Y, Mori M, Ishii H, Nagano H
  • Journal Title: Oncol Lett Volume: 6(2) Pages: 323-328
• [Journal Article] The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein. (2013)
  • Author(s): Kano Y
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 432 Issue: 1 Pages: 175-181
  • DOI: 10.1016/j.bbrc.2013.01.034
  • Peer Reviewed / Open Access
• [Journal Article] ErbB receptor tyrosine kinase/NF-κB signaling controls mammosphere formation in human breast cancer (2012)
  • Author(s): Hinohar a K, Kobayashi S, Kanauchi H, Shimizu S, Nishioka K, Tsuji E, Tada K, Umezawa K, Mori M, Ogawa T, Inoue J, Tojo A, Gotoh N
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Pages: 6584-6589
• [Journal Article] ErbB/NF-kB signaling controls mammosphere formation in human breast cancer (2012)
  • Author(s): Hinohara, K.
  • Journal Title: Proc.Natl.Acad.Sci Volume: (in press) Issue: 17 Pages: 6584-6589
  • DOI: 10.1073/pnas.1113271109
  • Peer Reviewed
• [Presentation] ErbB signaling regulates the mammosphere formation of breast cancer (2013)
  • Author(s): Hinohara K, Shimamura T, Fukuda H, Tominaga K, Kanauchi H, Niida A, Yamaguchi R, Imoto S, Tada K, Ogawa T, Miyano S, Gotoh N
  • Organizer: The 10th Japan Research Association For Immunotherapeutics
  • Place of Presentation: Japan
• [Presentation] A PI3K-dependent gene expression program that regulates mammosphere formation of breast cancer cells (2013)
  • Author(s): Hinohara K, Shimamura T, Fukuda H, Tominaga K, Kanauchi H, Niida A, Tada K, Ogawa T, Miyano S, Gotoh N
  • Organizer: The 11th Stem Cell Research Symposium
  • Place of Presentation: Japan
• [Presentation] Insulin-like growth factor signaling regulates breast cancer stem cell properties (2013)
  • Author(s): Hinohara K, Shimamura T, Kanauchi H, Niida A, Tuji E, Nishioka K, Tada K, Mori M, Ogawa T, Miyano S, Tojo A, Gotoh N
  • Organizer: The 72nd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Japan
• [Presentation] Insulin-like growth factor signaling regulates breast cancer stem cell properties (2013)
  • Author(s): Hinohara K, Shimamura T, Kanauchi H, Niida A, Tuji E, Nishioka K, Tada K, Mori M, Ogawa T, Miyano S, Tojo A, Gotoh N
  • Organizer: The 36th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Japan
• [Presentation] Insulin-like growth factor signaling regulates breast cancer stem cell properties. (2013)
  • Author(s): Hinohara K, Shimamura T, Kanauchi H, Niida A, Tuji E, Nishioka K, Tada K, Mori M, Ogawa T, Miyano S, Tojo A, Gotoh N.
  • Organizer: The 36th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: kobe
• [Presentation] Insulin-like growth factor signaling regulates breast cancer stem cell properties. (2013)
  • Author(s): Hinohara K, Shimamura T, Kanauchi H, Niida A, Tuji E, Nishioka K, Tada K, Mori M, Ogawa T, Miyano S, Tojo A, Gotoh N.
  • Organizer: The 72nd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: yokohama
• [Presentation] A PI3K-dependent gene expression program that regulates mammosphere formation of breast cancer cells. (2013)
  • Author(s): Hinohara K, Shimamura T, Fukuda H, Tominaga K, Kanauchi H, Niida A, Tada K, Ogawa T, Miyano S, Gotoh N.
  • Organizer: The 11th Stem Cell Research Symposium
  • Place of Presentation: tokyo
• [Presentation] A PI3K-dependent gene expression program that regulates mammosphere formation of breast cancer cells (2012)
  • Author(s): Hinohara K, Shimamura T, Kanauchi H, Niida A, Yamaguchi R, Imoto S, Ogawa T, Miyano S, Gotoh N
  • Organizer: The 71nd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Japan
• [Presentation] A PI3K-dependent gene expression program that regulates mammosphere formation of breast cancer cells (2012)
  • Author(s): Hinohara K, Shimamura T, Fukuda H, Tominaga K, Kanauchi H, Niida A, Yamaguchi R, Imoto S, Tada K, Ogawa T, Miyano S, Gotoh N
  • Organizer: The 35th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Japan
• [Presentation] ErbB/NF-κB signaling controls mammosphere formation in human breast cancer (2012)
  • Author(s): 日野原邦彦、小林誠一郎、金内一、梅澤一夫、森正樹、小川利久、井上純一郎、東條有伸、後藤典子
  • Organizer: 第10回幹細胞シンポジウム
  • Place of Presentation: 淡路島
• [Presentation] A PI3K-dependent gene expression program that regulates mammosphere formation of breast cancer cells (2012)
  • Author(s): 日野原邦彦、島村徹平、金内一、新井田厚司、山口類、井元清哉、小川利久、宮野悟、後藤典子
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] A PI3K-dependent gene expression program that regulates mammosphere formation of breast cancer cells (2012)
  • Author(s): 日野原邦彦、島村徹平、福田裕章、富永香菜、金内一、新井田厚司、山口類、井元清哉、多田敬一郎、小川利久、宮野悟、後藤典子
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] EGF receptor/ErbB-NFκB signaling for self-renewal of breast cancer stem cells (2011)
  • Author(s): Hinohara K, Kobayashi S, Umezawa K, Tojo A, Inoue J, Kanauchi H, Ogawa T, Gotoh N
  • Organizer: The 9th Stem Cell Research Symposium
  • Place of Presentation: Japan
• [Presentation] Heregulin-β1/ErbB signaling regulates self-renewal of breast cancer stem cells through activation of NF-κB (2011)
  • Author(s): Hinohara K, Kobayashi S, Umezawa K, Tojo A, Inoue J, Masaki Mori, Kanauchi H, Ogawa T, Gotoh N
  • Organizer: The 70nd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Japan
• [Presentation] ErbB/NF-κB signaling controls self-renewal of breast cancer stem cells (2011)
  • Author(s): Hinohara K, Kobayashi S, Umezawa K, Masaki Mori, Kanauchi H, Ogawa T, Inoue J, Tojo A, Gotoh N
  • Organizer: The 34th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Japan
• [Presentation] ErbB/NF-κB signaling controls mammosphere formation in human breast cancer (2011)
  • Author(s): Hinohara K, Kobayashi S, Kanauchi H, Umezawa K, Masaki Mori, Ogawa T, Inoue J, Tojo A, Gotoh N
  • Organizer: The 10th Stem Cell Research Symposium
  • Place of Presentation: Japan
• [Presentation] EGF receptor/ErbB-NFκB signaling for self-renewal of breast cancer stem cells
  • Author(s): 日野原邦彦
  • Organizer: 第9回幹細胞シンポジウム
  • Place of Presentation: 東京
• [Presentation] Heregulin-β1/ErbB signaling regulates self-renewal of breast cancer stem cells through activation of NF-κB
  • Author(s): 日野原邦彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] ErbB/NF-κB signaling controls self-renewal of breast cancer stem cells
  • Author(s): 日野原邦彦
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Book] 受容体型チロシンキナーゼErbBと転写因子NF-κBによる乳がん幹細胞維持の分子機構実験医学Vol.30 No.14 (9月号) (2012)
  • Author(s): 日野原邦彦、後藤典子
• [Book] 実験医学 カレントトピックス (2012)
  • Author(s): 日野原邦彦、後藤典子
  • Total Pages: 4
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/system-seimei/index.htm
• [Remarks] 研究室ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/system-seimei/index.htm