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Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth.
Nakahara, Ryuichi; Aki, Sho; Sugaya, Maki; Hirose, Haruka; Kato, Miki; Maeda, Keisuke; Sakamoto, Daichi M; Kojima, Yasuhiro; Nishida, Miyuki; Ando, Ritsuko; Muramatsu, Masashi; Pan, Melvin; Tsuchida, Rika; Matsumura, Yoshihiro; Yanai, Hideyuki; Takano, Hiroshi; Yao, Ryoji; Sando, Shinsuke; Shibuya, Masabumi; Sakai, Juro; Kodama, Tatsuhiko; Kidoya, Hiroyasu; Shimamura, Teppei; Osawa, Tsuyoshi.
Afiliación
  • Nakahara R; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Aki S; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Sugaya M; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Hirose H; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Kato M; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Maeda K; Department of Systems Biology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
  • Sakamoto DM; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Kojima Y; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Nishida M; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Ando R; Department of Systems Biology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
  • Muramatsu M; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Pan M; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Tsuchida R; Division of Molecular and Vascular Biology, IRDA, Kumamoto University, Kumamoto, Japan.
  • Matsumura Y; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Yanai H; Division of Nutriomics and Oncology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Takano H; Division of Metabolic Medicine, RCAST, The University of Tokyo, Tokyo, Japan.
  • Yao R; Department of Inflammology, RCAST, The University of Tokyo, Tokyo, Japan.
  • Sando S; Department of Cell Biology, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • Shibuya M; Department of Cell Biology, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • Sakai J; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Kodama T; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
  • Kidoya H; Institute of Physiology and Medicine, Jobu University, Takasaki, Japan.
  • Shimamura T; Division of Metabolic Medicine, RCAST, The University of Tokyo, Tokyo, Japan.
  • Osawa T; Division of Molecular Physiology and Metabolism, Graduate School of Medicine, Tohoku University, Sendai, Japan.
EMBO J ; 42(22): e114032, 2023 Nov 15.
Article en En | MEDLINE | ID: mdl-37781951
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Neoplasias Límite: Humans Idioma: En Revista: EMBO J Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Neoplasias Límite: Humans Idioma: En Revista: EMBO J Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido