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Signaling pathways in cancer‐associated fibroblasts: recent advances and future perspectives
Open accessAbstract
As a critical component of the tumor microenvironment (TME), cancer‐associated fibroblasts (CAFs) play important roles in cancer initiation and progression. Well‐known signaling pathways, including the transforming growth factor‐β (TGF‐β), Hedgehog (Hh), Notch, Wnt, Hippo, nuclear factor kappa‐B (NF‐κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen‐activated protein kinase (MAPK), and phosphoinositide 3‐kinase (PI3K)/AKT pathways, as well as transcription factors, including hypoxia‐inducible factor (HIF), heat shock transcription factor 1 (HSF1), P53, Snail, and Twist, constitute complex regulatory networks in the TME to modulate the formation, activation, heterogeneity, metabolic characteristics and malignant phenotype of CAFs. Activated CAFs remodel the TME and influence the malignant biological processes of cancer cells by altering the transcriptional and secretory characteristics, and this modulation partially depends on the regulation of signaling cascades. The results of preclinical and clinical trials indicated that therapies targeting signaling pathways in CAFs demonstrated promising efficacy but were also accompanied by some failures (e.g., NCT01130142 and NCT01064622). Hence, a comprehensive understanding of the signaling cascades in CAFs might help us better understand the roles of CAFs and the TME in cancer progression and may facilitate the development of more efficient and safer stroma‐targeted cancer therapies. Here, we review recent advances in studies of signaling pathways in CAFs and briefly discuss some future perspectives on CAF research.
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Self-citation
Cited by
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“Thus, the fibroblast–tumor cell interaction is not only context-dependent but also bidirectionally shaped by the evolving molecular and functional landscape of the tumor itself [33,34].”
Metadata
- Authors
- Fang, Z., Meng, Q., Xu, J., Wang, W., Zhang, B., Liu, J., Liang, C., Hua, J., Zhao, Y., Yu, X., & Shi, S.
- Venue
- Cancer Communications
- Published
- 2022-11-24
- Volume
- 43
- Issue
- 1
- Pages
- 3-41
- ISSN
- 1000-467X (ISSN-L)
- 2523-3548
- OpenAlex
- W4310079132
- Cited by
- 280
- References
- 397
- FWCI
- 14.22
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
