The role of ID protein family on proliferation and invasion of salivary gland cancer cells

• Project/Area Number: 15K11257
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyushu University
• Principal Investigator: SUMIDA TOMOKI 九州大学, 大学病院, 講師 (50314951)
• Co-Investigator(Kenkyū-buntansha): 森 悦秀 九州大学, 歯学研究院, 教授 (00231639) ; 山田 朋弘 九州大学, 歯学研究院, 准教授 (60335619) ; 中野 旬之 九州大学, 大学病院, 講師 (60511730)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ID1 / ID2 / 唾液腺癌 / 浸潤、転移 / Id2 / 扁平上皮癌 / 唾液腺腫瘍 / ホルモン療法 / IDタンパク / 性ステロイドホルモン / ID遺伝子ファミリー

Outline of Final Research Achievements

Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness.

Research Products

• [Int'l Joint Research] 1. California Pacific Medical Center/Research Institute(米国)
• [Int'l Joint Research]
• [Journal Article] Deregulation of Nicotinamide N-Methyltransferase and Gap Junction Protein Alpha-1 Causes Metastasis in Adenoid Cystic Carcinoma. (2018)
  • Author(s): Ishibashi K, Ishii K, Sugiyama G, Sumida T, Sugiura T, Kamata YU, Seki K, Fujinaga T, Kumamaru W, Kobayashi Y, Hiyake N, Nakano H, Yamada T, Mori Y.
  • Journal Title: Anticancer Res. Volume: 38 Pages: 187-197
  • Peer Reviewed
• [Journal Article] Regulation of β-Catenin Phosphorylation by PR55β in Adenoid Cystic Carcinoma. (2018)
  • Author(s): Ishibashi K, Ishii K, Sugiyama G, Kamata YU, Suzuki A, Kumamaru W, Ohyama Y, Nakano H, Kiyoshima T, Sumida T, Yamada T, Mori Y.
  • Journal Title: Cancer Genomics Proteomics. Volume: 15 Pages: 53-60
  • Peer Reviewed / Open Access
• [Journal Article] Estrogen Enhances Malignant Phenotypes in Human Salivary Adenoid Cystic Carcinoma Cells. (2016)
  • Author(s): Sumida T, Ishikawa A, Kamata YU, et al.
  • Journal Title: Anticancer Research Volume: 36 Pages: 2793-8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression (2016)
  • Author(s): Ryuichi Murase, Tomoki Sumida, Rumi Kawamura, Akiko Onishi-Ishikawa, Hiroyuki Hamakawa, Sean D. McAllister, Pierre-Yves Desprez.
  • Journal Title: Cancer letters Volume: 16 Issue: 1 Pages: 11-16
  • DOI: 10.1016/j.canlet.2016.04.021
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Id2が口腔扁平上皮癌細胞の増殖・浸潤に及ぼす影響 (2017)
  • Author(s): 鎌田 裕・住田知樹・石橋佳奈・小林洋輔・熊丸 渉・石井広太郎・中野旬之・山田朋弘・森 悦秀
  • Organizer: 第62回(公社)日本口腔外科学会総会・学術大会