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Cited by 113Autophagy in Disease and TherapyTGF-β signaling in diseasesCancer Cells and Metastasis

The effects and the mechanisms of autophagy on the cancer-associated fibroblasts in cancer

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Yan, Yuanliang, Chen, Xi, Wang, Xiang, Zhao, Zijin, Hu, Wenfeng, Zeng, Shuangshuang, Wei, Jie, Yang, Xue +5 more·2019·Journal of Experimental & Clinical Cancer Research
DOI 10.1186/s13046-019-1172-5PMC PMC6480893
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Abstract

Cancer-associated fibroblasts (CAFs) plays an essential role in cancer cell growth, metabolism and immunoreaction. Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. Targeting autophagy has gained interest with multiple preclinical and clinical trials, such as the pharmacological inhibitor chloroquine or the inducer rapamycin, especially in exploiting its ability to modulate the secretory capability of CAFs to enhance drug delivery or inhibit it to prevent its influence on cancer cell chemoresistance. In this review, we summarize the reports on autophagy in cancer-associated fibroblasts by detailing the mechanism and role of autophagy in CAFs, including the hypoxic-autophagy positive feedback cycle, the metabolic cross-talk between CAFs and tumors induced by autophagy, CAFs secreted cytokines promote cancer survival by secretory autophagy, CAFs autophagy-induced EMT, stemness, senescence and treatment sensitivity, as well as the research of antitumor chemicals, miRNAs and lncRNAs. Additionally, we discuss the evidence of molecules in CAFs that are relevant to autophagy and the contribution to sensitive treatments as a potential target for cancer treatment.

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  • CAFs serve as a metabolic source of nutrients for cancer cells by generating energy-rich metabolites such as ketones, lactate, and pyruvate that support mitochondrial oxidative phosphorylation in adjacent tumor cells.

    “In addition to structural remodeling, CAFs serve as metabolic source of nutrients for cancer cells. Tumor cells induce oxidative stress in adjacent fibroblasts, triggering the production of reactive oxygen species (ROS) [42,43,44]. This ROS burden initiates autophagic processes in fibroblasts, leading to the generation of energy-rich metabolites such as ketones, lactate, and pyruvate. These”

    From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [43]

    The Background section (‘The mechanism of CAFs autophagy’; page unavailable) says CAFs secrete ketones and lactate that fuel cancer-cell oxidative metabolism. It does not identify pyruvate as a secreted fuel: its discussion of pyruvate concerns pyruvate kinase, an enzyme linked to increased lactate and ketone output. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Yan, Y., Chen, X., Wang, X., Zhao, Z., Hu, W., Zeng, S., Wei, J., Yang, X., Qian, L., Zhou, S., Sun, L., Gong, Z., & Xu, Z.
Affiliations
  • Xiangya Hospital Central South University (CN)
  • Central South University (CN)
  • Hunan Provincial People's Hospital (CN)
Corresponding author
  • Gong, Zhicheng
  • Xu, Zhijie
ORCID
Venue
Journal of Experimental & Clinical Cancer Research
Publisher
Springer Science and Business Media LLC
Published
2019-04-23
Volume
38
Issue
1
Pages
171-171
ISSN
  • 0392-9078 (ISSN-L)
  • 1756-9966
DOI
10.1186/s13046-019-1172-5
PMC
PMC6480893
OpenAlex
W2944828587
Cited by
113
References
9
Citations by year
2026: 2 · 2025: 12 · 2024: 9 · 2023: 23 · 2022: 15 · 2021: 28 · 2020: 21 · 2019: 2 · 2018: 1
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (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 (81803035, 81572946, 81703036)
  • Youth Fund of Xiangya Hospital (2017Q17)
  • Postdoctoral Research Foundation of China (2017M610510)
  • Postdoctoral Science Foundation of Central South University (185702)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
autophagy, cancer-associated fibroblasts, tumor microenvironment, hypoxia, metabolic crosstalk, secretory autophagy, extracellular vesicles, epithelial-mesenchymal transition, cancer stemness, cellular senescence, chemoresistance, drug delivery, chloroquine, rapamycin, microRNA, long non-coding RNA, cancer therapy targets
MeSH terms
Cancer-Associated Fibroblasts, Autophagy, Cell Transformation, Neoplastic, Humans, Neoplasms, Drug Resistance, Neoplasm, MicroRNAs, Cell Proliferation, RNA, Long Noncoding

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