The DOI matches its Crossref record; 79 of the 81 references it cites were found in a registry or an index.
Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Open accessPublished version of a preprint
Abstract
Oncogenic KRAS (KRAS*) contributes to many cancer hallmarks. In colorectal cancer, KRAS* suppresses antitumor immunity to promote tumor invasion and metastasis. Here, we uncovered that KRAS* transforms the phenotype of carcinoma-associated fibroblasts (CAF) into lipid-laden CAFs, promoting angiogenesis and tumor progression. Mechanistically, KRAS* activates the transcription factor CP2 (TFCP2) that upregulates the expression of the proadipogenic factors BMP4 and WNT5B, triggering the transformation of CAFs into lipid-rich CAFs. These lipid-rich CAFs, in turn, produce VEGFA to spur angiogenesis. In KRAS*-driven colorectal cancer mouse models, genetic or pharmacologic neutralization of TFCP2 reduced lipid-rich CAFs, lessened tumor angiogenesis, and improved overall survival. Correspondingly, in human colorectal cancer, lipid-rich CAF and TFCP2 signatures correlate with worse prognosis. This work unveils a new role for KRAS* in transforming CAFs, driving tumor angiogenesis and disease progression, providing an actionable therapeutic intervention for KRAS*-driven colorectal cancer. Significance: This study identified a molecular mechanism contributing to KRAS*-driven colorectal cancer progression via fibroblast transformation in the tumor microenvironment to produce VEGFA driving tumor angiogenesis. In preclinical models, targeting the KRAS*–TFCP2–VEGFA axis impaired tumor progression, revealing a potential novel therapeutic option for patients with KRAS*-driven colorectal cancer. This article is featured in Selected Articles from This Issue, p. 2489
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“KRAS can alter the phenotype of CAFs, enriching them with lipids, which promotes angiogenesis and tumor progression.”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [26]
In the citing paper
“These lipid-enriched CAFs produce VEGFA, fostering angiogenesis and supporting tumor growth [26].”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [26]
In the citing paper
“KRAS activates the transcription factor CP2 (TFCP2), which then stimulates adipocyte differentiation factors, converting CAFs into lipid-rich cells.”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. (2022) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21708 · Cited by 17,196
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499
Improved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239
The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366
The Genomic Landscapes of Human Breast and Colorectal Cancers
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., et al. (2007) · Science · doi:10.1126/science.1145720 · Cited by 2,833
CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing
Labun, K., Montague, T. G., Krause, M., Cleuren, Y. N. T., Tjeldnes, H., & Valen, E. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz365 · Cited by 2,075
Type 2 alveolar cells are stem cells in adult lung
Barkauskas, C. E., Cronce, M. J., Rackley, C. R., Bowie, E. J., Keene, D. R., Stripp, B. R., Randell, S. H., Noble, P. W., & Hogan, B. L. M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68782 · Cited by 1,776
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer
Costa, A., Kieffer, Y., Scholer-Dahirel, A., Pelon, F., Bourachot, B., Cardon, M., Sirven, P., Magagna, I., Fuhrmann, L., Bernard, C., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.011 · Cited by 1,705
Cited by
Sorted by citations
Niu, N., Shen, X., Wang, Z., Chen, Y., Weng, Y., Yu, F., Tang, Y., Lu, P., Liu, M., Wang, L., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.03.005 · Cited by 244
Zhang, F., Ma, Y., Li, D., Wei, J., Chen, K., Zhang, E., Liu, G., Chu, X., Liu, X., Liu, W., et al. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01600-2 · Cited by 178
CAF-induced physical constraints controlling T cell state and localization in solid tumours
Arpinati, L., Carradori, G., & Scherz‐Shouval, R. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00740-4 · Cited by 162
The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy
Ma, Q., Zhang, W., Wu, K., & Shi, L. (2025) · Molecular Cancer · doi:10.1186/s12943-024-02218-1 · Cited by 101
Takeda, M., Yoshida, S., Inoue, T., Sekido, Y., Hata, T., Hamabe, A., Ogino, T., Miyoshi, N., Uemura, M., Yamamoto, H., et al. (2025) · Cancers · doi:10.3390/cancers17030428 · Cited by 82
“These lipid-enriched CAFs produce VEGFA, fostering angiogenesis and supporting tumor growth [26].”
Metadata
- Authors
- Hsu, W.-H., LaBella, K. A., Lin, Y., Xu, P., Lee, R., Hsieh, C.-E., Yang, L., Zhou, A., Blecher, J. M., Wu, C.-J., Lin, K., Shang, X., Jiang, S., Spring, D. J., Xia, Y., Chen, P., Shen, J. P., Kopetz, S., & DePinho, R. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- 3Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- ORCID
- Venue
- Cancer Discovery
- Published
- 2023-09-27
- Volume
- 13
- Issue
- 12
- Pages
- 2652-2673
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC10807546
- OpenAlex
- W4387115132
- Cited by
- 125
- References
- 81
- Citations by year
- 2026: 42 · 2025: 53 · 2024: 28 · 2023: 2
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas (RP210028)
- National Institutes of Health (F99 CA274661, R01 CA231360)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- oncogenic KRAS, colorectal cancer, cancer-associated fibroblasts, angiogenesis, VEGF-A, TFCP2, BMP4, Wnt5b, tumor microenvironment, tumor progression, antitumor immunity, prognostic signature, KRAS-targeted therapy
- MeSH terms
- Cancer-Associated Fibroblasts, Angiogenesis, Animals, Colonic Neoplasms, DNA-Binding Proteins, Fibroblasts, Humans, Lipids, Transcription Factors, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), Mice, Tumor Microenvironment
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
