The high-throughput screening to identify signaling pathways that are correlated with radioresistance of thyroid cancer stem cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861110
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Nagasaki University
• Principal Investigator: MATSUSE Michiko 長崎大学, 原爆後障害医療研究所, 助教 (30533905)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 甲状腺癌 / 放射線

Outline of Final Research Achievements

There is accumulating evidence that solid tumor contain cancer stem cells (CSC), which play important roles in cancer initiation, progression, recurrence and metastasis. In thyroid cancer (TC), anaplastic thyroid cancer (ATC) is highly aggressive and resistant to conventional chemo/radio-therapy. Although it is considered that these properties are associated with CSC population in TC, little is known about their characteristics. In this study, we conducted high-throughput screening using siRNA for 714 kinases with ATC cell lines to identify signaling pathways that are correlated with their sphere-forming ability, which is one of hallmarks of CSCs. The siRNAs for PDGFRβ, JAK3 and PIM1/3 markedly inhibited sphere formation. We also demonstrated that siRNA for STAT3/5 and inhibitors for JAK and NF-κB similarly suppressed the sphere-forming ability after irradiation. These data suggest that the JAK-STAT-NF-κB signaling pathway is critical for survival and radioresistance of TC-CSCs.

Free Research Field

甲状腺癌