ID | 116580 |
Title Alternative | 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
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Author |
Yoshimaru, Tetsuro
Tokushima University
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Matsushita, Yosuke
Tokushima University
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Aihara, Hitoshi
Tokushima University
Ono, Masaya
National Cancer Center Research Institute
Tsuneyama, Koichi
Tokushima University
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Sairyo, Koichi
Tokushima University
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Keywords | BIG3
mitochondria
osteosarcoma
peptide inhibitor
PHB2
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
Cancer Science
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ISSN | 13497006
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Publisher | Wiley|Japanese Cancer Association
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Volume | 112
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Issue | 10
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Start Page | 4208
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End Page | 4219
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Published Date | 2021-08-07
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Remark | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Shunichi Tokiの学位論文として提出され,学位審査・授与の対象となっている。 |
Rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License( https://creativecommons.org/licenses/by-nc/4.0/ ), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3561号
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Diploma Number | 甲医第1513号
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Granted Date | 2021-11-25
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
Institute of Advanced Medical Sciences
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