在肿瘤微环境中，脂肪细胞作为癌细胞的替代燃料来源。然而，脂肪细胞是否影响癌细胞的巨分子生物合成尚不清楚。本文采用多平台代谢组学、成像质谱、同位素追踪和基因表达分析，系统地揭示了原代人类脂肪细胞与卵巢癌（OvCa）细胞之间的双向相互作用。我们发现，在与脂肪细胞共培养和转移性肿瘤中的OvCa细胞中，部分来自糖酵解的葡萄糖用于甘油三磷酸（G3P）的生物合成。常氧下的HIF1α蛋白负责调节癌细胞中葡萄糖衍生碳源的改变流动，导致甘油磷脂和三酰甘油合成增加。HIF1α或G3P酰基转移酶3（甘油磷脂合成的调节酶）的沉默减少了OvCa异种移植模型中的转移。总之，我们发现在富含脂肪的肿瘤微环境中，癌细胞产生G3P作为关键膜和信号分子的前体，从而促进转移。针对特异于富含脂肪的肿瘤微环境的生物合成过程可能是一种有效的抗转移策略。© 2023. 作者（们）已授权转让给施普林格自然出版集团有限公司。

In the tumor microenvironment, adipocytes function as an alternate fuel source for cancer cells. However, whether adipocytes influence macromolecular biosynthesis in cancer cells is unknown. Here we systematically characterized the bidirectional interaction between primary human adipocytes and ovarian cancer (OvCa) cells using multi-platform metabolomics, imaging mass spectrometry, isotope tracing and gene expression analysis. We report that, in OvCa cells co-cultured with adipocytes and in metastatic tumors, a part of the glucose from glycolysis is utilized for the biosynthesis of glycerol-3-phosphate (G3P). Normoxic HIF1α protein regulates the altered flow of glucose-derived carbons in cancer cells, resulting in increased glycerophospholipids and triacylglycerol synthesis. The knockdown of HIF1α or G3P acyltransferase 3 (a regulatory enzyme of glycerophospholipid synthesis) reduced metastasis in xenograft models of OvCa. In summary, we show that, in an adipose-rich tumor microenvironment, cancer cells generate G3P as a precursor for critical membrane and signaling components, thereby promoting metastasis. Targeting biosynthetic processes specific to adipose-rich tumor microenvironments might be an effective strategy against metastasis.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.