論文 - 詳細
| RRC ID | 78766 |
|---|---|
| 著者 | Nakahara R, Aki S, Sugaya M, Hirose H, Kato M, Maeda K, Sakamoto DM, Kojima Y, Nishida M, Ando R, Muramatsu M, Pan M, Tsuchida R, Matsumura Y, Yanai H, Takano H, Yao R, Sando S, Shibuya M, Sakai J, Kodama T, Kidoya H, Shimamura T, Osawa T. |
| タイトル | Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth. |
| ジャーナル | EMBO J |
| Abstract |
Bone marrow-derived cells (BMDCs) infiltrate hypoxic tumors at a pre-angiogenic state and differentiate into mature macrophages, thereby inducing pro-tumorigenic immunity. A critical factor regulating this differentiation is activation of SREBP2-a well-known transcription factor participating in tumorigenesis progression-through unknown cellular mechanisms. Here, we show that hypoxia-induced Golgi disassembly and Golgi-ER fusion in monocytic myeloid cells result in nuclear translocation and activation of SREBP2 in a SCAP-independent manner. Notably, hypoxia-induced SREBP2 activation was only observed in an immature lineage of bone marrow-derived cells. Single-cell RNA-seq analysis revealed that SREBP2-mediated cholesterol biosynthesis was upregulated in HSCs and monocytes but not in macrophages in the hypoxic bone marrow niche. Moreover, inhibition of cholesterol biosynthesis impaired tumor growth through suppression of pro-tumorigenic immunity and angiogenesis. Thus, our findings indicate that Golgi-ER fusion regulates SREBP2-mediated metabolic alteration in lineage-specific BMDCs under hypoxia for tumor progression. |
| 巻・号 | 42(22) |
| ページ | e114032 |
| 公開日 | 2023-11-15 |
| DOI | 10.15252/embj.2023114032 |
| PMID | 37781951 |
| PMC | PMC10646561 |
| MeSH | Bone Marrow Cholesterol / metabolism Humans Hypoxia Monocytes* / metabolism Neoplasms* Sterol Regulatory Element Binding Protein 2 / genetics Sterol Regulatory Element Binding Protein 2 / metabolism |
| IF | 9.889 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB3683) BALL-1(RCB1882) |