FGFR inhibitors eliminate cancer stem-like cells in esophageal squamous cell carcinoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08943
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: Natsuizaka Mitsuteru 北海道大学, 医学研究院, 客員研究員 (80642446)
• Research Collaborator: MAEHARA Osamu 北海道大学, 生命科学院, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 食道扁平上皮癌 / 癌幹細胞 / CD44 / EMT / FGFR阻害剤 / MEK阻害剤

Outline of Final Research Achievements

In esophageal squamous cell carcinoma (ESCC), a subset of cells defined by high expression of CD44 and low expression of CD24 has been reported to be cancer stem-like cells (CSCs). Novel therapies directly targeting CSCs have the potential to improve prognosis of ESCC patients. We report that FGF-2 is significantly upregulated in CSCs and significantly increases CSC content in ESCC cell lines by inducing epithelial-mesenchymal transition (EMT). Conversely, the FGFR inhibitor sharply diminishes CSCs via induction of mesenchymal-epithelial transition (MET). Further experiments revealed that Mek/Erk pathway is crucial for FGF-2-mediated CSC regulation. Consistent with these findings in vitro, xenotransplantation studies demonstrated that inhibition of FGF-2-mediated FGFR/Erk signaling significantly delayed tumor growth. Inhibition of FGFR and/or Mek signaling represents a potential novel therapeutic option for targeting CSCs in ESCC.

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