Possible role of nuclear b-catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer

• Project/Area Number: 15K08385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kitasato University
• Principal Investigator: Takahashi Hiroyuki 北里大学, 医療衛生学部, 教授 (60377330)
• Research Collaborator: Saegusa Makoto 北里大学, 医学部, 教授 (00265711) ; Hashimura Miki ; Nakamura Kie ; Usami Akane
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌幹細胞 / 化学放射線療法 / 上皮間葉転換 / 直腸癌 / β-カテニン / 化学・放射線療法 / βーカテニン / がん幹細胞

Outline of Final Research Achievements

A total of 109 cases of locally advanced rectal cancer, along with a colon cancer cell line, were investigated. Nuclear β-catenin accumulation in pretreatment-biopsied samples was inversely associated with the therapeutic efficacy of chemoradiotherapy in resected rectal cancer. Nuclear β-catenin was predominantly observed in EMT-like lesions with decreased E-cadherin and increased Snail expression, along with expression of CSC-related markers. The EMT-like lesions also showed significant decreases in both apoptosis and cell proliferation. In-vitro, induced EMT/CSC properties together with nuclear β-catenin accumulation showed inhibition of cell proliferation and resistance to doxorubicin treatment.
Nuclear β-catenin accumulation may contribute to chemoradioresistance, probably through its regulation of EMT/CSC properties. In addition, nuclear β-catenin in pretreatment-biopsied samples is useful in predicting the efficacy of chemoradiotherapy in patients with rectal cancer.

Research Products

• [Journal Article] Identification of LEFTY as a molecular marker for ovarian clear cell carcinoma. (2017)
  • Author(s): Akiya M, Yamazaki M, Matsumoto T, Kawashima Y, Oguri Y, Kajita S, Kijima D, Chiba R, Yokoi A, Takahashi H, Kodera Y, Saegusa M.
  • Journal Title: Oncotarget Volume: 8 Issue: 38 Pages: 63646-63664
  • DOI: 10.18632/oncotarget.18882
  • Peer Reviewed / Open Access
• [Journal Article] Possible role of nuclear beta-catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer (2017)
  • Author(s): Hiroyuki Takahashi, Kie Nakamura, Akane Usami, Tomoko Tsuruta, Miki Hashimura, Toshihide Matsumoto, Makoto Saegusa
  • Journal Title: Histopathology Volume: 印刷中 Issue: 2 Pages: 227-237
  • DOI: 10.1111/his.13227
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] The role of nuclear beta-catenin in resistance to preoperative chemoradiotherapy in rectal carcinoma (2017)
  • Author(s): 高橋博之、橋村美紀、松本俊英、三枝信
  • Organizer: 第106回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2017-04-27
• [Presentation] 進行期直腸癌のb-カテニン/EMT誘導癌幹細胞化による化学・放射線療法の耐性機構の解析 (2017)
  • Author(s): 高橋博之，橋村美紀，松本俊英，三枝信
  • Organizer: 第106回日本病理学会総会
• [Presentation] 進行期直腸癌のβ-カテニン/EMT誘導癌幹細胞化による化学・放射線療法の耐性機構の解析 (2016)
  • Author(s): 高橋博之、宇佐美茜、千葉理紗子、橋村美紀、三枝 信
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-05-12
• [Presentation] 進行期直腸癌のb-カテニン/EMT誘導癌幹細胞化による化学・放射線療法の耐性機構の解析 (2015)
  • Author(s): 高橋博之、中村貴恵、鶴田智子、三枝 信
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30