The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3-PHB2 complex formation 10

• Material Type: 博士論文
• ISSN: 1349-7006
• Title: The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3-PHB2 complex formation
• Volume: 112 10
• Author/Editor: Toki, Shunichi; Yoshimaru, Tetsuro; Matsushita, Yosuke; Aihara, Hitoshi; Ono, Masaya; Tsuneyama, Koichi; Sairyo, Koichi; Katagiri, Toyomasa
• Author Heading: Toki, Shunichi; Yoshimaru, Tetsuro; Matsushita, Yosuke; Aihara, Hitoshi; Ono, Masaya; Tsuneyama, Koichi; Sairyo, Koichi; Katagiri, Toyomasa
• Publication, Distribution, etc.: Wiley|Japanese Cancer Association
• Publication Date: 2021-08-07
• Publication Date (W3CDTF): 2021-08-07
• Alternative Title: 骨肉腫細胞の生存と増殖はミトコンドリア局在BIG3-PHB2複合体形成に依存する
• Periodical title: Cancer Science
• Degree grantor/type: 徳島大学
• Date Granted: 2021-11-25
• Date Granted (W3CDTF): 2021-11-25
• Dissertation Number: 甲第3561号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3561号
• Text Language Code: eng
• Subject Heading: BIG3; mitochondria; osteosarcoma; peptide inhibitor; PHB2
• Target Audience: 一般
• Note (General): Previous studies reported the critical role of the brefeldin A–inhibited guanine nucleotide exchange protein 3–prohibitin 2 (BIG3-PHB2) complex in modulating estrogen signaling activation in breast cancer cells, yet its pathophysiological roles in osteosarcoma (OS) cells remain elusive. Here, we report a novel function of BIG3-PHB2 in OS malignancy. BIG3-PHB2 complexes were localized mainly in mitochondria in OS cells, unlike in estrogen-dependent breast cancer cells. Depletion of endogenous BIG3 expression by small interfering RNA (siRNA) treatment led to significant inhibition of OS cell growth. Disruption of BIG3-PHB2 complex formation by treatment with specific peptide inhibitor also resulted in significant dose-dependent suppression of OS cell growth, migration, and invasion resulting from G2/M-phase arrest and in PARP cleavage, ultimately leading to PARP-1/apoptosis-inducing factor (AIF) pathway activation–dependent apoptosis in OS cells. Subsequent proteomic and bioinformatic pathway analyses revealed that disruption of the BIG3-PHB2 complex might lead to downregulation of inner mitochondrial membrane protein complex activity. Our findings indicate that the mitochondrial BIG3-PHB2 complex might regulate PARP-1/AIF pathway-dependent apoptosis during OS cell proliferation and progression and that disruption of this complex may be a promising therapeutic strategy for OS.
• DOI: info:doi/10.1111/cas.15099; https://doi.org/info:doi/10.1111/cas.15099
• Persistent ID (NDL): info:ndljp/pid/11977169; https://dl.ndl.go.jp/pid/11977169
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2022-01-10T16:22:37+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/116580
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp