Role of Src family kinases in the Drug Resistance and Progression of Neuroblastoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kitasato University
• Principal Investigator: Ryuichi Sakai 北里大学, 医学部, 教授 (40215603)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 神経芽腫 / Src / パキシリン / p130Cas / dasatinib

Outline of Final Research Achievements

SFKs are known to be activated in various types of cancers and involved especially in the progression of the disease. The objective of this study is to elucidate the role of SFKs and their substrates in the progression of neuroblastoma. SFK inhibitors such as saracatinib, bosutinib and dasatinib generally caused more significant suppressive effects in cell migration than in cell proliferation in NB39-nu cells. Among SFK inhibitors, dasatinib showed outstanding inhibition of cell migration at the concentration as low as 10 nM. At this concentration, dasatinib caused inhibition of the phosphorylation of several substrates of SFKs such as paxillin and p130Cas. On the other hand, siRNA inhibition of these substrates did not show significant effect on the migration of NB39-nu.

Free Research Field

腫瘍生化学

Academic Significance and Societal Importance of the Research Achievements

神経芽腫は小児腫瘍の一つとしてがん遺伝子の活性化を引き起こす変異に乏しいにも関わらず高頻度で転移が見られ、また一方で1歳未満で発症する例では自然退縮を起こす症例があることから、転移に関わるチロシンキナーゼであるSrcファミリーの可逆的な活性化が関わっていることを考えている。Src阻害剤は神経芽腫の運動能や浸潤能を選択的に阻害し、増殖能に対する影響は限定的であることから、神経芽腫においても転移などの悪性化に関わる性質にSrcファミリーキナーゼが関わることが示唆された。将来的に進行した神経芽腫に対する適切なSrc阻害剤が有効である可能性が示された。