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Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review)

  • Authors:
    • Ruyue Li
    • Yintao Li
  • View Affiliations / Copyright

    Affiliations: School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China, Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 90
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    Published online on: August 25, 2025
       https://doi.org/10.3892/ijo.2025.5796
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Abstract

The occurrence and development of tumors is affected by tumor cells themselves and various components of the tumor microenvironment (TME). Among these, cancer‑associated fibroblasts (CAFs), the main stromal component, can differentiate from different cell types and play an important role in the TME. The present review summarized the role of the metabolic reprogramming of CAFs in tumor development and progression. As the rapid growth of tumors is a process inseparable from energy supply and the TME is characterized by hypoxia and nutrient deficiencies, metabolic reprogramming can reverse the effects of a lack of energy supply in the TME. Studies have found that CAFs can affect tumor proliferation, migration, invasion, metastasis and drug resistance by changing metabolic patterns. The present review promoted research on the metabolic reprogramming of CAFs and emphasized the importance of considering the heterogeneity and plasticity of CAFs in the TME, which will lead to the development of more effective therapeutic strategies that target specific metabolic pathways in CAFs, potentially improving the efficacy of cancer treatments and overcoming drug resistance.
View Figures

Figure 1

Illustration of the multiple cellular
sources of CAFs. The primary source of activated CAFs is NFs.
Additionally, the remaining cell types can differentiate into CAFs
in various ways to participate in tumor progression. For example,
bone marrow mesenchymal stem cells differentiate into CAFs through
recruitment. Epithelial and endothelial cells and macrophages can
be converted to CAFs through EMT, endothelial-mesenchymal
transition and macrophage-myofibroblast transition, respectively.
Smooth muscle cells and adipocytes are transdifferentiated into
CAFs. (Created in BioRender. Li, R. (2025) https://BioRender.com/s03n609.) CAF,
cancer-associated fibroblast; NF, normal fibroblast; EMT,
epithelial-mesenchymal transition; MMT, mesothelial-to-mesenchymal
transition; EndMT, endothelial-to-mesenchymal transition; MSC,
mesenchymal stem cell; SMC, smooth muscle cells.

Figure 2

Summary of functional CAF subtypes
predominantly found in PDAC and non-small cell lung,
gastrointestinal and breast cancers. (Created in BioRender. Li, R.
(2025) https://BioRender.com/24ea6hh.)
CAF, cancer-associated fibroblast; PDAC, pancreatic ductal
adenocarcinoma; iCAFs, inflammatory CAFs; myCAFs, myofibroblast
CAFs; apCAFs, antigen-presenting CAFs; meCAFs, metabolic CAFs;
tCAFs, tumor-like CAFs; mCAFs, matrix CAFs; ifnCAFs,
interferon-response CAFs; eCAFs, extracellular matrix CAFs; vCAFs,
vascular CAFs; mCAFs, matrix CAFs; cCAFs, cycling CAFs; dCAFs,
developmental CAFs; SSL CAFs, steady state-like CAFs; MR CAFs,
mechanoresponsive CAFs; IM CAFs, immunomodulatory CAFs.

Figure 3

Metabolic crosstalk between CAFs and
tumor cells. CAFs. CAF, cancer-associated fibroblast; GLUT, glucose
transporter; TCA cycle, tricarboxylic acid cycle; MCT,
monocarboxylate transporter; TGF-β, transforming growth
factor-beta; ITGB4, integrin subunit beta 4; LPC,
lysophosphatidylcholine; ATX, autotaxin; LPA, lysophosphatidic
acid; LPAR, lysophosphatidic acid receptor; RAS, rat sarcoma; MAPK,
mitogen-activated protein kinase; PI3K, phosphatidylinositol
3-kinase; Akt, Protein Kinase B (Created in BioRender. Li, R.
(2025) https://BioRender.com/wuur2w0).
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Copy and paste a formatted citation
Spandidos Publications style
Li R and Li Y: Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review). Int J Oncol 67: 90, 2025.
APA
Li, R., & Li, Y. (2025). Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review). International Journal of Oncology, 67, 90. https://doi.org/10.3892/ijo.2025.5796
MLA
Li, R., Li, Y."Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review)". International Journal of Oncology 67.5 (2025): 90.
Chicago
Li, R., Li, Y."Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review)". International Journal of Oncology 67, no. 5 (2025): 90. https://doi.org/10.3892/ijo.2025.5796
Copy and paste a formatted citation
x
Spandidos Publications style
Li R and Li Y: Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review). Int J Oncol 67: 90, 2025.
APA
Li, R., & Li, Y. (2025). Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review). International Journal of Oncology, 67, 90. https://doi.org/10.3892/ijo.2025.5796
MLA
Li, R., Li, Y."Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review)". International Journal of Oncology 67.5 (2025): 90.
Chicago
Li, R., Li, Y."Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review)". International Journal of Oncology 67, no. 5 (2025): 90. https://doi.org/10.3892/ijo.2025.5796
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