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Cited by 262TGF-β signaling in diseasesCancer, Hypoxia, and MetabolismCancer, Lipids, and Metabolism

TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

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Shi, Xueke, Yang, Jin, Deng, Shuzhi, Xu, Hongdan, Wu, Deyang, Zeng, Qingxiang, Wang, Shimeng, Hu, Tao +2 more·2022·Journal of Hematology & Oncology
DOI 10.1186/s13045-022-01349-6PMC PMC9482317
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Abstract

Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-β signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an “engine” of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-β signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-β ligands act as an “endocrine” cytokine and influence host metabolism. Therefore, having insight into the role of TGF-β signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-β to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-β-dependent mechanism reprogramming, paving the way for TGF-β-related antitumor therapy from the perspective of metabolism.

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  • TGFβ1 promotes the infiltration of CAFs.

    “Prior studies have also indicated that TGFβ1 is both a key product and a major stimulant of CAFs, promoting the accumulation of CAFs and the deposition of the ECM 47,48.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [47]

    The section on TGF-β-dependent stromal–epithelial coupling (page unavailable) says TGF-β1 induces normal fibroblasts to become CAFs and increases collagen synthesis. This supports CAF formation and a component of ECM deposition, but it does not establish that TGF-β1 promotes CAF infiltration into tumors. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • TGFβ1 is the primary subtype of TGF in the TME and plays a crucial role in forming a non-inflamed TME.

    “Notably, TGFβ1 is the primary subtype of TGF in the TME and plays a crucial role in forming a non-inflamed TME.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [47]

    The Background (page unavailable) identifies TGF-β1 as one of three TGF-β ligands but does not say it is the primary subtype in the TME. The ‘Immune cells–epithelia metabolism coupling’ section (page unavailable) says TGF-β signaling contributes to an immunosuppressive TME, but does not specifically attribute formation of a non-inflamed TME to TGF-β1. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Sorted by citations

Authors
Shi, X., Yang, J., Deng, S., Xu, H., Wu, D., Zeng, Q., Wang, S., Hu, T., Wu, F., & Zhou, H.
Affiliations
Sichuan University (CN)
Corresponding author
  • Wu, Fanglong
  • Zhou, Hongmei
ORCID
Venue
Journal of Hematology & Oncology
Publisher
Springer Science and Business Media LLC
Published
2022-09-17
Volume
15
Issue
1
Pages
135-135
ISSN
1756-8722 (ISSN-L)
DOI
10.1186/s13045-022-01349-6
PMC
PMC9482317
OpenAlex
W4296139756
Cited by
262
References
27
Citations by year
2026: 66 · 2025: 105 · 2024: 59 · 2023: 29 · 2022: 3
FWCI
5.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Hematology & Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82071124, No. 82071124, 82002884, 82101028)
  • Natural Science Foundation of Sichuan Province (2022NSFSC1599)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
TGF-beta signaling, tumor metabolic reprogramming, immunosuppressive tumor microenvironment, tumor progression, treatment resistance, metastasis
MeSH terms
Carcinogens, Humans, Ligands, Neoplasms, Transforming Growth Factors, Transforming Growth Factor beta, Tumor Microenvironment

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