Investigation on usefulness of Fes / Fer as new therapeutic target and predictive factor in urothelial cancer

• Project/Area Number: 15K10594
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagasaki University
• Principal Investigator: TAKEHARA Kosuke 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (40580345)
• Co-Investigator(Kenkyū-buntansha): 宮田 康好 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (60380888) ; 望月 保志 長崎大学, 病院(医学系), 准教授 (40404256)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: Fes / 尿路癌 / 癌細胞増殖 / 癌細胞浸潤 / 予後 / TUBB3 / 化学療法 / 膀胱癌 / 細胞増殖 / 細胞浸潤 / 細胞遊走 / 遊走能 / Fer / T24

Outline of Final Research Achievements

In T24 cell which is urothelial cancer (UC) cell with high malignant potential, Fes knock-down (KD) lead to significantly suppression of cancer cell proliferation, invasion and migration (P = 0.003, 0.018, and <0.001, respectively). Such significant change by Fes-KD was not detected in 5637 and RT4 cell. In 2013 bladder cancer (BC) patients, there was no significant relationship between Fes expression and muscle invasive status. However, in patients with high grade cancer, Fes expression in muscle invasive BC (MIBC) was significantly higher (P = 0.002) than that in non-MIBC (NMIBC), and its was positively correlated to cell proliferation (P = 0.002). In addition, Fes expression was significantly associated with metastasis-free survival in high grade BC　(P = 0.021). On the other hand, class III beta-tubulin （TUBB3）, which is Fes/Fer-related molecule, was useful predictor for anti-cancer effects of second-line paclitaxel-based chemotherapy for patients with cisplatin-resistant UC.

Research Products

• [Journal Article] Pathological significance and prognostic significance of FES expression in bladder cancer vary according to tumor grade. (2018)
  • Author(s): Asai A, Miyata Y, Takehara K, Kanda S, Watanabe SI, Greer PA, Sakai H.
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: １４４ Issue: 1 Pages: 21-31
  • DOI: 10.1007/s00432-017-2524-1
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Class III Beta-tubulin Predicts Prognosis in Patients with Cisplatin-resistant Bladder Cancer Receiving Paclitaxel-based Second-line Chemotherapy. (2018)
  • Author(s): Miyata Y, Matsuo T, Nakamura Y, Yasuda T, Ohba K, Takehara K, Sakai H.
  • Journal Title: Anticancer Research Volume: 38 Pages: 1629-1635
  • Peer Reviewed / Open Access
• [Presentation] Pathological significance and prognostic roles of FES expression in bladder cancer (2017)
  • Author(s): Akihiro Asai, Yasuyoshi Miyata, Kosuke Takehara, Shigeru Kanda, Shin-ichi Watanabe, Hideki Sakai
  • Organizer: European Association of Urology, Annual Meeting 2017
  • Place of Presentation: ロンドン（イギリス）
  • Year and Date: 2017-03-24
  • Int'l Joint Research