β3-Integrin controls pericyte metabolic states and shapes tumour-stromal metabolic crosstalk in breast cancer
In the authors' words
Pericytes are emerging as dynamic regulators of the tumour microenvironment. Yet, their role in tumour metabolism remains elusive. Here, we investigate whether {beta}3-integrin regulates pericyte metabolic state and shapes stromal-tumour metabolic interactions in breast cancer. By integrating spatial and single-cell transcriptomics from human breast tumours with multi-omics profiling of tumour-derived pericytes in vitro, we identify two {beta}3-integrin-dependent metabolic states. {beta}3-integrin-high pericytes display a metabolically active phenotype characterised by increased glycolysis and enhanced de novo serine/glycine synthesis, supporting collagen production. In contrast, {beta}3-integrin loss induces a lipid-associated state, marked by neutral lipid accumulation and lipid droplets. Mechanistically, {beta}3-integrin regulates this metabolic switch via mTOR signalling. Importantly, these states extend beyond pericytes, with adjacent cancer cells shifting towards fatty acid oxidation and lipid use near {beta}3-integrin-low pericytes. Together, our findings establish {beta}3-integrin as a key metabolic switch in pericytes and highlight their role in driving tumour metabolic plasticity.
Appeared: Saturday, September 26. bioRxiv. Preprint, not yet peer-reviewed.