Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth

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, results 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 mac

SUBMITTER: Mr. Ryuichi Nakahara 

PROVIDER: S-SCDT-10_15252-EMBJ_2023114032 | biostudies-other |

REPOSITORIES: biostudies-other