Identification of ALK-related ovarian cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15092
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kitasato University
• Principal Investigator: Inoue Hisako 北里大学, 医学部, 講師 (20813504)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ALK / 卵巣がん / 神経内分泌

Outline of Final Research Achievements

ALK immunoreactivity was significantly higher in high-grade serous carcinoma(HGSC) and was significantly associated with several unfavorable clinicopathological factors. HGSC cell lines stably overexpressing ALK exhibited increased cell proliferation, enhanced cancer stem cell features, and accelerated cell mobility, whereas these phenotypes were abrogated in ALK-knockdown (KD) cells. Expression of ELAVL3(HuC), as well as Sox2 and Sox3, were significantly increased in cells overexpressing ALK. Overexpression of Sox2 or Sox3 also enhanced both ALK and ELAVL3 promoter activities. Finally, ALK overexpression was due to increased expression of neuroendocrine markers including synaptophysin, CD56, and BCL2 in HGCS tissues. These findings suggest that overexpression of full-length ALK may influence the biological behavior of HGSC through cooperation with ELAVL3 and Sox factors, leading to establishment and maintenance of the aggressive phenotypic characteristics of HGSC.

Free Research Field

分子病理学

Academic Significance and Societal Importance of the Research Achievements

①卵巣癌を「ALK遺伝子関連情報伝達異常」という観点からその生物学的特性、特にEMT/癌幹細胞化機構との関連性を分子病理学的に解析し、ALK関連卵巣癌という新たなカテゴリーを提唱する。②卵巣癌のALK発現と臨床病理学的因子との関連性から新たな予後予測システムを構築する。③ALK阻害剤などの分子標的薬や小化学化合物によるALK陽性卵巣癌の新規治療法開発の基盤を築く。