Functional analysis of CD133in tumorigenesis and stemness of cancer stem cell

• Project/Area Number: 21790397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: SHIMOZATO Osamu 千葉県がんセンター(研究所), 発がん研究グループ, 上席研究員 (30344063)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌 / 発生・分化 / 癌性幹細胞 / CD133

Research Abstract

CD133is a putative cancer stem cell marker of several malignancies but its roles still remain unclear. We here examined roles of CD133in tumorigenesis and stemness of human colon cancer cells. Knocked-down of CD133retarded tumor formation of colon cancer cells in nude mice and suppressed anchorage-independent cell growth. CD133-knockdown reduced transactivation activity ofβ-catenin resulting from AKT inactivation ; subsequently accelerated the enterocyte differentiation of colon cancer cells upon sodium butyrate treatment. Furthermore, we found a novel transcriptional regulation of CD133gene by GATA6transcription factor, which is bound to the upstream region of exon2of CD133gene. These data collectively suggest that CD133is involved in keeping undifferentiated-status and tumorigenesis of colon cancer.

Research Products

• [Journal Article] Expression of a murine homolog of apoptosis-inducing human IL-24/MDA-7 in murine tumors fails to induce apoptosis or produce anti-tumor effects (2012)
  • Author(s): Nagakawa H, Shimozato O, 他9名
  • Journal Title: Cellular Immunol Volume: 275 Issue: 1-2 Pages: 90-97
  • DOI: 10.1016/j.cellimm.2012.02.010
  • Peer Reviewed
• [Journal Article] CD133 suppresses neuroblastoma cell differentiation via signal pathway modification (2011)
  • Author(s): Takenobu H, Shimozato O, Nakamura T, Ochiai H, Yamaguchi Y, Ohira M, Nakagawara A, Kamijo T
  • Journal Title: Oncogene Volume: 30 Issue: 1 Pages: 97-105
  • DOI: 10.1038/onc.2010.383
  • Peer Reviewed
• [Journal Article] Bmi1 regulates cell fate via tumor suppressor WWOX repression in small cell lung cancer cells (2011)
  • Author(s): Kimura M, Takenobu H, Akita N, Nakazawa A, Ochiai H, Shimozato O, Fujimura YI, Koseki H, Yoshino I, Kimura H, Nakagawara A, Kamijo T
  • Journal Title: Cancer Sci Volume: 102 Issue: 5 Pages: 983-990
  • DOI: 10.1111/j.1349-7006.2011.01891.x
  • NAID: 10029293384
  • Peer Reviewed
• [Journal Article] CD70 is selectively expressed on Th1 but not on Th2 cells and is required for Th1-type immune responses (2011)
  • Author(s): Kawamura T, 他1名、Shimozato O, 他6名
  • Journal Title: J Invest Dermatol Volume: 131 Issue: 6 Pages: 1252-1261
  • DOI: 10.1038/jid.2011.36
  • Peer Reviewed
• [Journal Article] CD133 suppresses neuroblastoma cell differentiation via signal pathway modification. (2011)
  • Author(s): Takenobu H, Shimozato O, Nakamura T, Ochiai H, Yamaguchi Y, Ohira M, Nakagawara A, Kamijo T.
  • Journal Title: Oncogene Volume: 30 Pages: 97-105
  • Peer Reviewed
• [Presentation] CD133plays roles in keeping the undifferentiated status of human colon cancer cells via PI3K/AKT activation (2011)
  • Author(s): 下里修(他5名)
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] CD133 plays roles in keeping the undifferentiated status of human colon cancer cells via PI3K/AKT activation (2011)
  • Author(s): 下里修, 他5名
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Tumor sphere specific CD133 regulation in neuroblastoma (2011)
  • Author(s): 竹信尚典、下里修, 他5名
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] Acquired multi-drug resistance in human colon cancer cells by sphere Formation (2011)
  • Author(s): 中島久美子、下里修, 他4名
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-03
• [Presentation] GATA-6transactivates a novel promoter for stem cell marker CD133gene in human colorectal cancer cells (2010)
  • Author(s): 下里修(他5名)
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-23
• [Presentation] GATA-6 transactivates a novel promoter for stem cell marker CD133 gene in human colorectal cancer cells. (2010)
  • Author(s): 下里修, (他5名)
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-23
• [Presentation] CD 133 regulates neuroblastoma stemness via p38MAPK and PI3K/Akt activation. (2010)
  • Author(s): 竹信尚典、下里修, (他5名)
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-23
• [Presentation] 幹細胞マーカーCD133分子はβ-cateninの制御を通じて大腸がん細胞の腫瘍形成を亢進する (2009)
  • Author(s): 下里修(他5名)
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市パシフィコ横浜
  • Year and Date: 2009-10-01
• [Presentation] 幹細胞マーカーCDI33分子はβ-cateninの制御を通じて大腸がん細胞の腫瘍形成を亢進する (2009)
  • Author(s): 下里修
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市パシフィコ横浜
  • Year and Date: 2009-10-01