トリプルネガティブ型乳がんにおけるCYLD発現低下の生物学的意義

• Published in: 日本薬理学会年会要旨集 p. 1-Y-E3-2
• Main Authors: 桑野, 明香里, 平井, ちか, 末永, 尚輝, 金丸, 歩美, 新垣, ひとみ, 林, 光博, 西郷, 智香, 齋藤, 秀之, 城野, 博史
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: cancer; gene; oncogene; subtype
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_1-Y-E3-2

Purpose: Tumor suppressor cylindromatosis (CYLD) regulates various cell signaling pathways, such as nuclear factor-kB (NF-kB), as its aberrant activation contributes to malignant progression. Although we showed that loss of CYLD expression in triple breast cancer (TNBC), the most aggressive breast cancer type, contributed to poor prognosis, the roles of CYLD expression in TNBC remain unknown. In this study, we evaluated the biological significance of CYLD expression in the malignant progression of TNBC in terms of cell migration and drug resistance.Methods: To assess the biological roles of CYLD in TNBC, we knocked-down CYLD expression by CYLD-specific siRNA. Cell migration and anti-tumor drug sensitivity were evaluated by transwell assay and cell counting assay, respectively. Results: CYLD down-regulation significantly promoted cell migration, drug resistances (Epirubicin, Docetaxel, 5-FU) via NF-kB activation. Moreover, the cell migration and anchorage-independent growth promoted by CYLD down-regulation were significantly suppressed by NF-kB inhibitor.Conclusion: In TNBC, CYLD down-regulation may contribute to the malignant progression, such as, promoting cell migration via NF-kB activation, suggesting that NF-kB inhibitor may be effective for CYLD down-regulated TNBC patients with poor prognosis.