# Cancer-associated fibroblasts as key regulators of lipid metabolism in the tumour microenvironment

**Authors:** Jessamy Adams, Caterina M. Suelzu, Gabriele Strusi, Justin Stebbing

PMC · DOI: 10.1038/s41388-026-03733-9 · 2026-03-21

## TL;DR

This paper reviews how cancer-associated fibroblasts influence lipid metabolism in tumors, which could lead to new cancer treatments.

## Contribution

The paper highlights the emerging role of cancer-associated fibroblasts in regulating lipid metabolism across different cancer types.

## Key findings

- CAFs can produce, secrete, and internalize lipids in the tumor microenvironment.
- Different CAF subtypes may have opposing roles in lipid metabolism depending on cancer type.
- Lipid metabolism in CAFs is influenced by external factors like obesity and diet.

## Abstract

Alterations in metabolism are recognised as a hallmark of cancer, allowing for rapid proliferation in an environment often hypoxic and short of nutrients. Cells within the tumour microenvironment (TME) often undergo metabolic alterations to adapt to these conditions, and this can also contribute to tumour progression. Cancer associated fibroblasts (CAFs) are amongst the most abundant non-cancerous cells in the TME and the main cells responsible for production and maintenance of the extracellular matrix. However, CAF subtypes can impact tumours in different ways and have been shown to play a role in alterations to lipid metabolism within tumours, being able to produce and secrete lipids, internalise them from the surrounding environment, and undergo fatty acid oxidation. Whilst this is still an emerging area of research, it appears that CAFs can have opposing roles in lipid metabolism in different types of cancer. Understanding the different metabolic pathways utilised in both CAFs and cancer cells and how external factors such as obesity and high fat diets influence them, could provide novel treatment avenues in the future. This review explores the literature surrounding lipid metabolism in CAFs and how this influences tumour progression and treatment resistance.

## Full-text entities

- **Genes:** Bmp2 (bone morphogenetic protein 2) [NCBI Gene 12156] {aka Bmp2a}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Bmp4 (bone morphogenetic protein 4) [NCBI Gene 12159] {aka Bmp-4, Bmp2b, Bmp2b-1, Bmp2b1}, Plat (plasminogen activator, tissue) [NCBI Gene 18791] {aka D8Ertd2e, tPA}, Acc (anterior capsular cataract) [NCBI Gene 104371], Abca8b (ATP-binding cassette, sub-family A member 8b) [NCBI Gene 27404] {aka Abca8}, Acta2 (actin alpha 2, smooth muscle, aorta) [NCBI Gene 11475] {aka 0610041G09Rik, Actvs, SMAalpha, SMalphaA, a-SMA, alphaSMA}, Wnt5b (wingless-type MMTV integration site family, member 5B) [NCBI Gene 22419] {aka Wnt-5b}, Spp1 (secreted phosphoprotein 1) [NCBI Gene 20750] {aka 2AR, Apl-1, BNSP, BSPI, Bsp, ETA-1}, Kras (Kras proto-oncogene, GTPase) [NCBI Gene 16653] {aka K-Ras, K-Ras 2, K-ras, Ki-ras, Kras-2, Kras2}, Caf (caffeine susceptibility) [NCBI Gene 104272], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Eln (elastin) [NCBI Gene 13717] {aka E030024M20Rik}, Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, Scd1 (stearoyl-Coenzyme A desaturase 1) [NCBI Gene 20249] {aka Scd, Scd-1, ab}, Mmp7 (matrix metallopeptidase 7) [NCBI Gene 17393] {aka MAT, MMP-7}, Fasn (fatty acid synthase) [NCBI Gene 14104] {aka A630082H08Rik, FAS}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Abca8a (ATP-binding cassette, sub-family A member 8a) [NCBI Gene 217258], Acly (ATP citrate lyase) [NCBI Gene 104112] {aka A730098H14Rik}, Fabp3 (fatty acid binding protein 3, muscle and heart) [NCBI Gene 14077] {aka Fabph-1, Fabph-4, Fabph1, Fabph4, H-FABP, Mdgi}, Srebf2 (sterol regulatory element binding factor 2) [NCBI Gene 20788] {aka SREBP-2, SREBP2, SREBP2gc, bHLHd2, lop13, nuc}, Fabp5 (fatty acid binding protein 5, epidermal) [NCBI Gene 16592] {aka E-FABP, Fabpe, Klbp, PA-FABP, mal1}, Setd2 (SET domain containing 2) [NCBI Gene 235626] {aka 4921524K10Rik, KMT3A}
- **Diseases:** breast cancer (MESH:D001943), FAO (MESH:C536560), hypoxic (MESH:D002534), inflammation (MESH:D007249), adipose (MESH:D018205), HNSCC (MESH:D000077195), angina (MESH:D000787), undifferentiated (MESH:C580334), metabolic disorders (MESH:D008659), melanoma (MESH:D008545), vessel dysfunction (MESH:C536223), weight-loss (MESH:D015431), CAFs (MESH:D009369), fibrosis (MESH:D005355), overweight (MESH:D050177), hypoxia (MESH:D000860), HCC (MESH:D006528), gastric cancer (MESH:D013274), pancreatic cancer (MESH:D010190), CRC (MESH:D015179), insulin resistance (MESH:D007333), endometrial cancer (MESH:D016889), PDAC (MESH:D021441), Obesity (MESH:D009765), TNBC (MESH:D064726), lung cancer (MESH:D008175), peritoneal metastasis (MESH:D010538), lung metastasis (MESH:D009362), prostate cancer (MESH:D011471)
- **Chemicals:** simvastatin (MESH:D019821), ND-646 (MESH:C000621677), steroid (MESH:D013256), acetyl-CoA (MESH:D000105), SB-204990 (MESH:C112852), eicosapentaenoic acid (MESH:D015118), Oleic acid (MESH:D019301), Fatostatin (MESH:C545733), glucose (MESH:D005947), gemcitabine (MESH:D000093542), free fatty acids (MESH:D005230), Unsaturated fatty acids (MESH:D005231), orlistat (MESH:D000077403), vemurafenib (MESH:D000077484), Pitavastatin (MESH:C108475), palmitic acid (MESH:D019308), olive oil (MESH:D000069463), omega-3 fatty acid (MESH:D015525), sphingolipid (MESH:D013107), progesterone (MESH:D011374), stearic acid (MESH:C031183), malonyl-CoA (MESH:D008316), Etomoxir (MESH:C054207), gold (MESH:D006046), fat (MESH:D005223), Lipid (MESH:D008055), ketones (MESH:D007659), FAO (-), LA (MESH:D019787), cholesterol (MESH:D002784), monounsaturated fatty acids (MESH:D005229), ALA (MESH:D000409), acids (MESH:D000143), oxygen (MESH:D010100), TVB-2640 (MESH:C000717092), perhexiline (MESH:D010480), lactate (MESH:D019344), Fatty acids (MESH:D005227)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Cercopithecidae (monkey, family) [taxon 9527]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13033449/full.md

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Source: https://tomesphere.com/paper/PMC13033449