ArticleEBioMedicine2026
Spatial membrane lipid remodelling encodes epithelial lineage and state in human colon cancer.
Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCancer progression is driven by spatially organised intratumoural heterogeneity, yet the molecular basis of this organisation remains incompletely understood. While spatial transcriptomics has advanced rapidly, the spatial architecture and functional relevance of tumour lipid metabolism remain poorly characterised. We aimed to resolve whether membrane phospholipid remodelling is spatially organised across epithelial cell states in human colon cancer.
methodsWe developed an integrative spatial multi-omic strategy linking mass spectrometry imaging to transcriptome-defined cellular states on consecutive tissue sections from primary and intraperitoneal metastatic human colon cancer specimens. Epithelial lipid phenotypes were characterised, validated in an independent cohort, and linked to transcriptional programmes.
findingsWe identified four spatially organised epithelial lipid phenotypes defined by membrane phospholipid composition. These phenotypes aligned with transcriptional programmes reflecting epithelial lineage and differentiation state, and were organised along a differentiation axis marked by coordinated remodelling of arachidonic acid-, oleic acid-, and linoleic acid-containing phospholipids. Secretory-associated states, enriched in metastatic lesions, showed increased DHA-containing phospholipids and activation of peroxisomal pathways. Lipid phenotype assignments were reproducible across an independent cohort.
interpretationMembrane phospholipid composition encodes biologically meaningful epithelial cell states within human tumours, establishing lipid remodelling as a structured and spatially organised dimension of tumour heterogeneity.
fundingThis study was supported by the ISCIII (PI19/00002, PI24/00313), the Health Research Institute of the Balearic Islands (IMP22/04), the Government of the Balearic Islands (AP_2021_001), the Basque Government (IT1491-22), the European Regional Development Fund, and the Scientific Foundation, Spanish Association Against Cancer (INVES222995RODR).
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