論文 - 詳細
| RRC ID | 72201 |
|---|---|
| 著者 | Toki S, Yoshimaru T, Matsushita Y, Aihara H, Ono M, Tsuneyama K, Sairyo K, Katagiri T. |
| タイトル | The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3-PHB2 complex formation. |
| ジャーナル | Cancer Sci |
| Abstract |
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. |
| 巻・号 | 112(10) |
| ページ | 4208-4219 |
| 公開日 | 2021-10-1 |
| DOI | 10.1111/cas.15099 |
| PMID | 34363714 |
| PMC | PMC8486206 |
| MeSH | Animals Apoptosis / physiology Apoptosis Inducing Factor / metabolism Bone Neoplasms / metabolism Bone Neoplasms / pathology* Bone Neoplasms / therapy Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Cell Proliferation / physiology* Cell Survival / physiology* Cell-Penetrating Peptides / pharmacology Databases, Factual Down-Regulation G2 Phase Cell Cycle Checkpoints Gene Silencing Guanine Nucleotide Exchange Factors / drug effects Guanine Nucleotide Exchange Factors / metabolism Guanine Nucleotide Exchange Factors / physiology* Humans M Phase Cell Cycle Checkpoints Membrane Proteins / metabolism Mice Mice, Nude Mitochondria / metabolism* Mitochondrial Membranes / metabolism Neoplasm Invasiveness Neoplasm Transplantation Osteosarcoma / metabolism Osteosarcoma / pathology* Osteosarcoma / therapy Poly (ADP-Ribose) Polymerase-1 / metabolism Prohibitins RNA, Small Interfering / metabolism Repressor Proteins / drug effects Repressor Proteins / metabolism Repressor Proteins / physiology* |
| IF | 4.966 |
| リソース情報 | |
| ヒト・動物細胞 | Saos-2(RCB0428) |