The DOI matches its Crossref record; 65 of the 69 references it cites were found in a registry or an index.
Oncogenic collagen I homotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer
Open accessAbstract
In contrast to normal type I collagen (Col1) heterotrimer (α1/α2/α1) produced by fibroblasts, pancreatic cancer cells specifically produce unique Col1 homotrimer (α1/α1/α1). Col1 homotrimer results from epigenetic suppression of the Col1a2 gene and promotes oncogenic signaling, cancer cell proliferation, tumor organoid formation, and growth via α3β1 integrin on cancer cells, associated with tumor microbiome enriched in anaerobic Bacteroidales in hypoxic and immunosuppressive tumors. Deletion of Col1 homotrimers increases overall survival of mice with pancreatic ductal adenocarcinoma (PDAC), associated with reprograming of the tumor microbiome with increased microaerophilic Campylobacterales, which can be reversed with broad-spectrum antibiotics. Deletion of Col1 homotrimers enhances T cell infiltration and enables efficacy of anti-PD-1 immunotherapy. This study identifies the functional impact of Col1 homotrimers on tumor microbiome and tumor immunity, implicating Col1 homotrimer-α3β1 integrin signaling axis as a cancer-specific therapeutic target.
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“Targeted deletion of type I collagen from SMA-expressing fibroblasts increases immune suppressive myeloid infiltration, accelerating tumor progression166”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [166]
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Self-citationMUC16 drives macrophage-mediated immunosuppression in pancreatic cancer
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Metadata
- Authors
- Chen, Y., Yang, S., Tavormina, J., Tampe, D., Zeisberg, M., Wang, H., Mahadevan, K. K., Wu, C.-J., Sugimoto, H., Chang, C.-C., Jenq, R. R., McAndrews, K. M., & Kalluri, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Kalluri, Raghu
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 40
- Issue
- 8
- Pages
- 818-834.e9
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC9831277
- OpenAlex
- W4286267917
- Cited by
- 289
- References
- 69
- Citations by year
- 2026: 48 · 2025: 82 · 2024: 100 · 2023: 49 · 2022: 10
- FWCI
- 26.79
- 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, 372 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)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- Sid W. Richardson Foundation (P30CA016672)
- National Cancer Institute (P01CA117969, P30CA16672)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- alpha3beta1 integrin, pancreatic ductal adenocarcinoma, tumor microbiome, Bacteroidales, Campylobacterales, tumor hypoxia, immunosuppression, T cell infiltration, anti-PD-1 therapy, antitumor immunity, tumor organoids, tumor cell proliferation
- MeSH terms
- Animals, Collagen, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Collagen Type I, Integrin alpha3beta1, Mice, Carcinogenesis, Microbiota
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