Identification of Lung Cancer Stem Cell Markers

• Project/Area Number: 23659664
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: Nagoya University
• Principal Investigator: SUZUKI Motoshi 名古屋大学, 医学系研究科, 講師 (80236017)
• Co-Investigator(Kenkyū-buntansha): KATO Seiichi 名古屋大学, 医学系研究科, 助教 (30584669) ; USAMI Noriyasu 名古屋大学、愛知県がんセンター中央病院, 医学部付属病院、呼吸器外科, 助教、医長 (30378179)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 癌幹細胞 / マーカー / 肺癌 / がん幹細胞 / 分子標的

Research Abstract

By using clinical specimens, we performed IHC analysis for the putative cancer-initiating cell markers. Among the markers, we found CD166 may be the mostuseful one. To identify novel lung cancer-initiating cell markers, we analyzed an open database, screened genes that were highly expressed in CD166-positive cells, measured expression levels of such genes in the clinical specimens, and performed shRNA-induced knocking-down experiments. We identified that a gene could be a novel lung cancer-initiating cell marker, as well as a future target for the cancer treatment.

Research Products

• [Journal Article] Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB (2013)
  • Author(s): Mizutani N, Kobayashi M, Sobue S, Ichihara M, Ito H, Tanaka K, Iwaki S, Fujii S, Ito Y, Tamiya-Koizumi K, Takagi A, Kojima T, Naoe T, Suzuki M, Nakamura M, Banno Y, Nozawa Y, Murate T
  • Journal Title: Biochim Biophys Acta
  • Peer Reviewed
• [Journal Article] Aberrant DNA replication in Cancer (2013)
  • Author(s): Suzuki M, Takahashi T
  • Journal Title: Mutat Res, Fund Mol Mech Mutat
  • Peer Reviewed
• [Journal Article] Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB (2013)
  • Author(s): Mizutani N
  • Journal Title: Biochim Biophys Acta Volume: 未定
  • Peer Reviewed
• [Journal Article] a transcriptional target of TTF-1, inhibits ROCK1, and reduces cell motilityand metastasis (2012)
  • Author(s): Hosono Y, Yamaguchi T, Mizutani E, Yanagisawa K, Arima C, Tomida S, Shimada Y, Hiraoka M, Kato S, Yokoi K, Suzuki M, Takahashi T. MYBPH
  • Journal Title: EMBO J Volume: 31 Pages: 481-493
  • Peer Reviewed
• [Journal Article] Role of down-regulated neutral ceramidase during all-trans retinoic acid induced neuronal differentiation in SH-SY5Y neuroblastoma cells (2012)
  • Author(s): Tanaka K, Tamiya-Koizumi K, Hagiwara K, Ito H, Takagi A, Kojima T, Suzuki M, Iwaki S, Fujii S, Nakamura M, Banno Y, Kannagi R, Tsurumi T, Kyogashima M, Murate T
  • Journal Title: J Biochem Volume: 151 Pages: 611-620
  • NAID: 10031166103
  • Peer Reviewed
• [Journal Article] Role of down-regulated neutral ceramidase during all-trans retinoic acid induced neuronal differentiation in SH-SY5Y neuroblastoma cells (2012)
  • Author(s): Ito H, Tanaka K, Hagiwara K, Kobayashi M, Mizutani N, Takagi A, Kojima T, Sobue S, Ichihara M, Suzuki M, Tamiya-Koizumi K, Nakamura M, Banno Y, Nozawa Y, Murate T
  • Journal Title: J Biochem Volume: 151 Pages: 599-610
  • NAID: 10031166103
  • Peer Reviewed
• [Journal Article] Hybrid liposomes affect cellular lipid constituents and caveolae structures (2012)
  • Author(s): Cao K, Tanaka K, Komizu Y, Tamiya-Koizumi K, Murate T, Ueoka R, Kyogashima M, Usukura J, Takahashi T, Suzuki M
  • Journal Title: Bioorg Med Chem Lett Volume: 22 Pages: 1731-1733
  • Peer Reviewed
• [Journal Article] NKX2-1/ TITF1/ TTF-1- Induced ROR1 Is Required to Sustain EGFR Survival Signaling in Lung Adenocarcinoma (2012)
  • Author(s): Yamaguchi T, Yanagisawa K, Sugiyama R, Hosono Y, Shimada Y, Arima C, Kato S, Tomida S, Suzuki M, Osada H, Takahashi T
  • Journal Title: Cancer Cell Volume: 20 Pages: 348-361
  • Peer Reviewed
• [Journal Article] MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility (2012)
  • Author(s): Hosono Y, Usukura J, Yamaguchi T, Yanagisawa K, Suzuki M, Takahashi T
  • Journal Title: Biochem Biophys Res Commun Volume: 428 Pages: 173-178
  • Peer Reviewed
• [Journal Article] Involvement of KRAS G12A mutation in theIL-2-independent growth of a human T-LGL leukemia cell line, PLT-2 (2012)
  • Author(s): Mizutani N, Ito H, Hagiwara K, Kobayashi M, Hoshikawa A, Nishida Y, Takagi A, Kojima T, Suzuki M, Osawa Y, Ohnishi K, Daibata M, Murate T
  • Journal Title: Nagoya J Med Sci Volume: 74 Pages: 261-271
  • Peer Reviewed
• [Journal Article] Involvement of KRAS G12A mutation in the IL-2-independent growth of a human T-LGL leukemia cell line, PLT-2 (2012)
  • Author(s): Mizutani N
  • Journal Title: Nagoya J Med Sci Volume: 74 Pages: 261-271
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of neutral sphingomyelinase 2 in all-trans retinoic acid-treated human breast cancer cell line, MCF-7. (2012)
  • Author(s): Ito H
  • Journal Title: J Biochem. Volume: 151 Issue: 6 Pages: 599-610
  • DOI: 10.1093/jb/mvs037
  • Peer Reviewed
• [Journal Article] Role of down-regulated neutral ceramidase during all-trans retinoic acid induced neuronal differentiation in SH-SY5Y neuroblastoma cells (2012)
  • Author(s): Kouji Tanaka
  • Journal Title: J.Biochem. Volume: (印刷中) Issue: 6 Pages: 611-620
  • DOI: 10.1093/jb/mvs033
  • Peer Reviewed
• [Journal Article] NKX2-1/TITF1/TTF-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma (2012)
  • Author(s): Yamaguchi T, et al
  • Journal Title: Cancer Cell Volume: 21 Issue: 3 Pages: 348-361
  • DOI: 10.1016/j.ccr.2012.02.008
  • Peer Reviewed
• [Journal Article] Hybrid liposomes affect cellular lipid constituents and caveolae structures (2012)
  • Author(s): Cao K
  • Journal Title: Bioorg Med Chem Lett Volume: 22 Issue: 4 Pages: 1731-1733
  • DOI: 10.1016/j.bmcl.2011.12.093
  • Peer Reviewed
• [Journal Article] MYBPH, a transcriptional target of TTF-1, inhibits ROCK1, and reduces cell motility and metastasis (2012)
  • Author(s): Hosono Y, et al
  • Journal Title: EMBO Journal Volume: 31 Issue: 2 Pages: 481-493
  • DOI: 10.1038/emboj.2011.416
  • Peer Reviewed
• [Journal Article] Proteasomal Non-catalytic Subunit PSMD2 as a Potential Therapeutic Target in Association with Various Clinicopathologic Features in Lung Adenocarcinomas (2011)
  • Author(s): Matsuyama Y, Suzuki M, Arima C, Huang Q, Tomida S, Takeuchi T, Sugiyama R, Itoh Y, Yatabe Y, Goto H, Takahashi T
  • Journal Title: Mol Carcinog Volume: 50 Pages: 301-309
  • Peer Reviewed
• [Journal Article] Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription. (2011)
  • Author(s): Murakami M, Ito H, Hagiwara K, Kobayashi M, Hoshikawa A, Takagi A, Kojima T, Tamiya-Koizumi K, Sobue S, Ichihara M, Suzuki M, Banno Y, Nozawa Y, Murate T
  • Journal Title: J Cell Biochem Volume: 112 Pages: 3449-3458
  • Peer Reviewed
• [Journal Article] Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas. (2011)
  • Author(s): Matsuyama Y, Suzuki M, Arima C, Huang QM, Tomida S, Takeuchi T, Sugiyama R, Itoh Y, Yatabe Y, Goto H, Takahashi T.
  • Journal Title: 10.1002/mc.20632 Volume: 50 Pages: 301-309
  • Peer Reviewed
• [Presentation] A pivotal role of CerS6 on the ceramide metabolic pathways and tumor metastasis in lung cancer (2012)
  • Author(s): Motoshi Suzuki, Ke Cao, Kouji Tanaka, Seiichi Kato, Chinatsu Arima, Yasuyuki Hosono, Kiyoshi Yanagisawa, Keiko Tamiya-Koizumi, Takashi Murate, Mamoru Kyogashima and Takashi Takahashi
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] HYBRID LIPOSOMES MAY TARGET THE HIGH EXPRESSION LEVELS OF CERS6 IN CANCER CELLS (2012)
  • Author(s): Cao K, Komizu Y, Tanaka K, Arima C, Tamiya-Koizumi K, Kyogashima M, Ueoka R, Takahashi T and Suzuki M
  • Organizer: The 5th International Symposium on "Molecular Science of Fluctuations toward Biological Functions"
  • Place of Presentation: Nara
• [Presentation] A pivotal role of CerS6 on the ceramide metabolic pathways and HL-induced apoptosis in lung cancer (2012)
  • Author(s): Suzuki M
  • Organizer: The 6th International Symposium on "Molecular Science of Fluctuations toward Biological Functions"
  • Place of Presentation: Kyoto
• [Presentation] A pivotal role of CerS6 on the ceramide metabolic pathways and tumor metastasis in lung cancer (2012)
  • Author(s): Suzuki M
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ホテルロイトン札幌（札幌）
• [Presentation] A pivotal role of CerS6 on the ceramide metabolic pathways and tumor metastasis in lung cancer (2012)
  • Author(s): Suzuki M
  • Organizer: The 6th International Symposium on "Molecular Science of Fluctuations toward Biological Functions
  • Place of Presentation: 京都テルサ（京都）
• [Presentation] Targeting the high expression levels of CerS6 in cancer (2011)
  • Author(s): Suzuki M
  • Organizer: The 7th International Forum on Oxidative Stress and Aging
  • Place of Presentation: Gdansk, Poland
  • Year and Date: 2011-11-26
• [Presentation] Regulation of DNA polymerase subunit POLD4 influences genomic instability in lung cancer (2011)
  • Author(s): Suzuki M, Tomida S, Arima C, Cao K, Masuda Y, Kamiya K, Osadaa H, Yatabe Y and Takahashi T
  • 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
• [Presentation] Hybrid liposomes may target the high expression levels of CerS6 in cancer cells (2011)
  • Author(s): Ke Cao, Yuji Komizu, Kouji Tanaka, Chinatsu Arima, Keiko Tamiya-Koizumi, Mamoru Kyogashima, Ryuichi Ueoka, Takashi Takahashi and Motoshi Suzuki
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Hybrid liposomes may target the high expression levels of CerS6 in cancer cells (2011)
  • Author(s): Cao K, Komizu Y, Tanaka K, Arima C, Tamiya-Koizumi K, Kyogashima M, Ueoka R, Takahashi T and Suzuki M
  • Organizer: The 4th International Symposium of Nagoya Univ GCOE
  • Place of Presentation: Nagoya
• [Presentation] Regulation of DNA polymerase subunit POLD4 influences genomic instability in lung cancer. (2011)
  • Author(s): Suzuki M, Tomida S, Arima C, Cao K, Masuda Y, Kamiya K, Osadaa H, Yatabe Y and Takahashi T.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Hybrid liposomes may target the high expression levels of CerS6 in cancer cells. (2011)
  • Author(s): Cao K, Komizu Y, Tanaka K, Arima C, Tamiya-Koizumi K, Kyogashima M, Ueoka R, Takahashi T and Suzuki M.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Targeting the high expression levels of CerS6 in cancer (2011)
  • Author(s): Suzuki M
  • Organizer: The 7th International Forum on Oxidative Stress and Aging(招待講演)
  • Place of Presentation: Gdansk
• [Book] DOJIN BIOSCIENCE「生体分子の動きを探る:揺らぎと生体機能」 (2013)
  • Author(s): 鈴木元
  • Publisher: 化学同人
• [Book] 生体分子の動きを探る：揺らぎと生体機能 (2013)
  • Author(s): 寺嶋 正秀
  • Publisher: 揺らぎから見たがん治療のメカニズム
• [Book] 癌細胞イラストレーテッド (2011)
  • Author(s): 鈴木元、高橋隆
  • Publisher: 羊土社
• [Book] 癌細胞イラストレーテッド がんとmicroRNA (2011)
  • Author(s): 鈴木元、高橋隆
  • Total Pages: 8
  • Publisher: 羊土社
• [Patent(Industrial Property Rights)] Thermostable polymerases having altered fidelity and method of identifying and using same (2013)
  • Inventor(s): Loeb LA, Hood L and Suzuki M 権利者:U. Washington
  • Industrial Property Rights Holder: U. Washington
  • Filing Date: 2013-03-12
  • Overseas
• [Patent(Industrial Property Rights)] Thermostable polymerases having altered fidelity and method of identifying and using same (2013)
  • Inventor(s): Loeb LA, Hood L and Suzuki M
  • Industrial Property Rights Holder: U. washington
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-03-12
  • Overseas