Sox2 is a novel target gene for the treatment of lung squamous cell carcinoma.

• Project/Area Number: 25462188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kawasaki Medical School
• Principal Investigator: Fukazawa Takuya 川崎医科大学, 医学部, 講師 (20379845)
• Co-Investigator(Kenkyū-buntansha): NAOMOTO YOSHIO 川崎医科大学, 医学部, 教授 (00237190) ; YAMATSUJI TOMOKI 川崎医科大学, 医学部, 准教授 (40379730) ; TAKAOKA MUNENORI 川崎医科大学, 医学部, 講師 (50548568)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肺扁平上皮癌 / Sox2遺伝子

Outline of Final Research Achievements

Sox2 is a pluripotency controller that was recently identified as a novel oncogene, recurrently activated in lung squamous cell carcinoma (SCC). Inhibition of Sox2 by siRNA suppresses cell viability and colony formation of Sox2 expressing EBC2 and LK2 lung SCC cells. Moreover, Sox2 siRNA inhibits lung SCC growth in vivo in a xenograft mouse model derived from these cells. Cell cycle analysis showed that Sox2 silencing significantly increased the G1 population in the cells. We used biological studies to demonstrate that CDKN1A was suppressed by Sox2 in lung SCC cells. G1 cell cycle arrest induced by Sox2 siRNA was rescued by CDKN1A siRNA. These results indicate that targeting Sox2 is an effective strategy for the treatment of Sox2-expressing lung SCC and the tumorigenic effect of Sox2 in lung SCC cells is mediated in part by suppression of CDKN1A.

Research Products

• [Journal Article] SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma. (2016)
  • Author(s): Fukazawa T, Guo M, Ishida N, Yamatsuji T, Takaoka M, Yokota E, Haisa M, Miyake N, Ikeda T, Okui T, Takigawa N, Maeda Y, Naomoto Y.
  • Journal Title: Scientific Reports Volume: 6 Pages: 20113-20113
  • Peer Reviewed
• [Presentation] 人工転写因子を用いた肺扁平上皮癌に対する新規標的療法の開発 (2015)
  • Author(s): 横田 悦子1、深澤 拓也1、山辻 知樹1、高岡 宗徳1、羽井佐 実1、三 宅 規子2、池田 智子2、石田 尚正1、吉田 将和1、瀧川 奈義夫3、世 良 貴史4、猶本 良夫1 (1 川崎医科大学・総合外科、2 川崎病院研究セ ンター、3 川崎医科大学・総合内科 4、4 岡山大学・生命工学・生体機 能分子設計)
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-10