The identification of the oral cancer stem cell and analysis of the property―Role analysis of the epigenetic regulation and application to treatment―

• Project/Area Number: 21390541
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: SHINOHARA Masanori 熊本大学, 大学院・生命科学研究部, 教授 (90117127)
• Co-Investigator(Kenkyū-buntansha): HIRAKI Akimitsu 熊本大学, 大学院・生命科学研究部, 講師 (60404034) ; NAKAYAMA Hideki 熊本大学, 大学院・生命科学研究部, 助教 (70381001)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
• Keywords: 癌幹細胞 / DNA メチル化異常 / エピジェネティクス / がん抑制遺伝子 / 口腔扁平上皮癌 / 転移 / 薬剤耐性 / 口腔癌 / 扁平上皮癌 / 浸潤

Research Abstract

The importance of DNA methylation in the transcriptional silencing of tumor suppressor genes is recognized in cancer stem cell. Genome-wide hypomethylation has also been reported in cancer stem cell and has been associated with genetic instability. In this study, we analyzed methylation of tumor suppressor gene of oral squamous cell carcinoma. The results suggest that epigenetic inactivation of tumor suppresser gene play an important role in pathogenesis of cancer stem cell and many genes may be a useful molecular target for the diagnosis and treatment for cancer stem cell.

Research Products

• [Journal Article] Selective inhibition of NF-kB by NBD peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma (2012)
  • Author(s): Tanaka T., Nakayama H., Yoshitake Y., Irie A., Nagata M., Kawahara K., Takamune Y., Yoshida R., Nakagawa Y., Ogi H., Shinriki S., Ota K., Hiraki A., Ikebe T., Nishimura Y., Shinohara M
  • Journal Title: Cancer Sci Volume: 103 Pages: 455-463
• [Journal Article] Downregulation of midkine induces cisplatin resistance in human oral squamous cell carcinoma (2012)
  • Author(s): Ota T, Jono H, Ota K, Shinriki S, Ueda M, Sueyoshi T, Nakatani K, Hiraishi Y, Wada T, Fujita S, Obayashi K,Shinohara M, Ando Y
  • Journal Title: Oncol Rep. Volume: 27 Pages: 1674-1680
• [Journal Article] Quantitative assessment of higher-order chromatin structure of the INK4/ARF locus in human senescent cells (2012)
  • Author(s): Hirosue A, Ishihara K, Tokunaga K, Watanabe T, Saitoh N, Nakamoto M, Chandra T, Narita M, Shinohara M, Nakao M
  • Journal Title: Aging Cell Volume: 11(3) Pages: 553-556
• [Journal Article] Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma (2011)
  • Author(s): Shinriki S, Jono H, Ueda M, Ota K, Ota T, Sueyoshi T, Oike Y, Ibusuki M, Hiraki A, Nakayama H, Shinohara M, Ando Y
  • Journal Title: J Pathol Volume: 225 Pages: 142-150
• [Journal Article] Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in oral squamous cell carcinoma (2011)
  • Author(s): Nagata M, Nakayama H, Tanaka T, Yoshida R, Yoshitake Y, Fukuma D, KOta K, awahara K, Nakagawa Y, Hiraki A, Shinohara M
  • Journal Title: Br J Cancer Volume: 105 Pages: 1322-1330
• [Journal Article] Nucleostemin affects the proliferation but not differentiation of oral squamous cell carcinoma cells (2011)
  • Author(s): Ito T, Yoshida R, Fujimoto,T, Kudoh S, Nagata M, Nakayama H, Shinohara M
  • Journal Title: Cancer Science Volume: 102 Pages: 1418-1423
  • NAID: 10029295726
• [Journal Article] Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma (2010)
  • Author(s): Ota K., Fujimori H., Ueda M., Jono H., Shinriki S., Ota T., SueyoshiT., Taura M., Taguchi A., Kai H., Shinohara M., Ando Y
  • Journal Title: Int J Oncol Volume: 37 Pages: 397-808
• [Journal Article] Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and vivo growth of human oral squamous cell carcinoma (2009)
  • Author(s): Shinriki S., Jono H., Ota K., Ueda M., Kudo M., Ota T., Oike Y., Endo M., Ibusuk M., Hiraki A., Nakayama H., Yoshitake Y.,Shinohara M., Ando Y
  • Journal Title: Clin Cancer Res Volume: 15 Pages: 5426-5434