Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-κB-Dependent Manner
Open accessAbstract
Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin carcinogenesis, we found a proinflammatory gene signature in CAFs isolated from dysplastic skin. This signature was maintained in CAFs from subsequent skin carcinomas and was evident in mammary and pancreatic tumors in mice and in cognate human cancers. The inflammatory signature was already activated in CAFs isolated from the initial hyperplastic stage in multistep skin tumorigenesis. CAFs from this pathway promoted macrophage recruitment, neovascularization, and tumor growth, activities that are abolished when NF-kappaB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be "educated" by carcinoma cells to express proinflammatory genes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tumor cells actively reprogram surrounding fibroblasts into cancer-associated fibroblasts (CAFs).
“With the advancement of tumor biology, it became clear that tumor cells actively reprogram surrounding fibroblasts into a modified state termed cancer-associated fibroblasts (CAFs) [5,19,35,36].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [36]
CAFs are key contributors to ECM remodeling, angiogenesis, and metastasis.
“These CAFs are characterized by the expression of specific markers, such as desmin and fibroblast activation protein, and are now recognized as key contributors to ECM remodeling, angiogenesis, and metastasis [36,37,38,39,40].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [36]
Various inflammatory modulators can promote CAF activation, with IL-1 acting through NF-κB and IL-6 acting primarily on STAT transcription factors.
“Various inflammatory modulators can promote CAF activation, with interleukin-1 (IL-1) acting through NF-κB and IL-6 acting primarily on signal transducer and activator of transcription (STAT) transcription factors57,58.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [57]
The citation lists haven’t been fetched yet
References 85 · Cited by 1,515
- Authors
- Erez, N., Truitt, M., Olson, P., & Hanahan, D.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Hanahan, Douglas
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 17
- Issue
- 2
- Pages
- 135-147
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2169281418
- Cited by
- 1,515
- References
- 85
- Citations by year
- 2026: 41 · 2025: 76 · 2024: 92 · 2023: 83 · 2022: 97 · 2021: 131 · 2020: 133 · 2019: 119 · 2018: 94 · 2017: 108 · 2016: 113 · 2015: 90 · 2014: 89 · 2013: 79 · 2012: 66
- FWCI
- 34.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1753 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute (T32 CA09043)
- Cancer Research Institute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- cancer-associated fibroblasts, tumor-promoting inflammation, NF-κB signaling, hyperplasia, macrophage recruitment, neovascularization, tumor growth, dermal fibroblasts, mammary tumors, pancreatic tumors, tumor microenvironment
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Uterine Cervical Neoplasms, Female, Fibroblasts, Humans, Mammary Neoplasms, Experimental, Mice, Transgenic, Neoplasms, Neovascularization, Pathologic, Skin Neoplasms, Gene Expression Regulation, Neoplastic, NF-kappa B, Inflammation Mediators, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review
