Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion

Timothy Budden; Noah Palombo; Shilpa Gurung; Martha  Gutteridge; Charlotte Russell; Jair Marques; Alex von Kriegsheim; Lyutong  An; Catherine Harwood; Louisa Motta; Claus Jørgensen; Carlos Lopez-Garcia; Gaudy Gaudy-Marqueste; Kevin Harrington; Malin Pedersen; Ben O'Leary; Antonio Rullan; Amaya Viros

doi:10.1038/s42255-026-01514-y

Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion

Timothy Budden
, Noah Palombo
, Shilpa Gurung
, Martha Gutteridge
, Charlotte Russell
, Jair Marques
, Alex von Kriegsheim
, Lyutong An
, Catherine Harwood
, Louisa Motta
, Claus Jørgensen
, Carlos Lopez-Garcia
, Gaudy Gaudy-Marqueste
, Kevin Harrington
, Malin Pedersen
, Ben O'Leary
, Antonio Rullan
, Amaya Viros

North Wales Medical School

Cancer Research UK Manchester Institute
Liverpool University
Ediburgh Cancer Research
University of Edinburgh
Barts and the London School of Medicine and Dentistry
Salford Royal Hospital
Aix-Marseille University
Institute of Cancer Research

Research output: Contribution to journal › Article › peer-review

Abstract

Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide–sphingosine-1-phosphate–STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion

Original language	English
Journal	Nature Metabolism
Early online date	27 Apr 2026
DOIs	https://doi.org/10.1038/s42255-026-01514-y
Publication status	Published - 27 Apr 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1038/s42255-026-01514-yLicence: CC BY

s42255-026-01514-yFinal published version, 15.6 MBLicence: CC BY

Cite this

Budden, T., Palombo, N., Gurung, S., Gutteridge, M., Russell, C., Marques, J., von Kriegsheim, A., An, L., Harwood, C., Motta, L., Jørgensen, C., Lopez-Garcia, C., Gaudy-Marqueste, G., Harrington, K., Pedersen, M., O'Leary, B., Rullan, A., & Viros, A. (2026). Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion. Nature Metabolism. https://doi.org/10.1038/s42255-026-01514-y

@article{0fd28afb85724c968a76269b3971b37d,

title = "Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion",

abstract = "Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide–sphingosine-1-phosphate–STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion",

author = "Timothy Budden and Noah Palombo and Shilpa Gurung and Martha Gutteridge and Charlotte Russell and Jair Marques and \{von Kriegsheim\}, Alex and Lyutong An and Catherine Harwood and Louisa Motta and Claus J{\o}rgensen and Carlos Lopez-Garcia and Gaudy Gaudy-Marqueste and Kevin Harrington and Malin Pedersen and Ben O'Leary and Antonio Rullan and Amaya Viros",

year = "2026",

month = apr,

day = "27",

doi = "10.1038/s42255-026-01514-y",

language = "English",

journal = "Nature Metabolism",

issn = "2522-5812",

publisher = "Nature Research",

}

Budden, T, Palombo, N, Gurung, S, Gutteridge, M, Russell, C, Marques, J, von Kriegsheim, A, An, L, Harwood, C, Motta, L, Jørgensen, C, Lopez-Garcia, C, Gaudy-Marqueste, G, Harrington, K, Pedersen, M, O'Leary, B, Rullan, A & Viros, A 2026, 'Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion', Nature Metabolism. https://doi.org/10.1038/s42255-026-01514-y

TY - JOUR

T1 - Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion

AU - Budden, Timothy

AU - Palombo, Noah

AU - Gurung, Shilpa

AU - Gutteridge, Martha

AU - Russell, Charlotte

AU - Marques, Jair

AU - von Kriegsheim, Alex

AU - An, Lyutong

AU - Harwood, Catherine

AU - Motta, Louisa

AU - Jørgensen, Claus

AU - Lopez-Garcia, Carlos

AU - Gaudy-Marqueste, Gaudy

AU - Harrington, Kevin

AU - Pedersen, Malin

AU - O'Leary, Ben

AU - Rullan, Antonio

AU - Viros, Amaya

PY - 2026/4/27

Y1 - 2026/4/27

N2 - Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide–sphingosine-1-phosphate–STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion

AB - Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide–sphingosine-1-phosphate–STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion

U2 - 10.1038/s42255-026-01514-y

DO - 10.1038/s42255-026-01514-y

M3 - Article

SN - 2522-5812

JO - Nature Metabolism

JF - Nature Metabolism

ER -

Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this