The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression
Open accessAbstract
Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.
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Cites
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“Rather, the elevated tissue mechanics directly activate key pathways such as integrin-dependent signaling and YAP to promote tumor progression and aggression 10–12 .”
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Hippo Pathway Activity Influences Liver Cell Fate
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KRAS and YAP1 Converge to Regulate EMT and Tumor Survival
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de Visser, K. E., & Joyce, J. A. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.016 · Cited by 4,059
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Every step of the way: integrins in cancer progression and metastasis
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Metadata
- Authors
- Laklai, H., Miroshnikova, Y. A., Pickup, M. W., Collisson, E. A., Kim, G. E., Barrett, A. S., Hill, R. C., Lakins, J. N., Schlaepfer, D. D., Mouw, J. K., LeBleu, V. S., Roy, N., Novitskiy, S. V., Johansen, J. S., Poli, V., Kalluri, R., Iacobuzio-Donahue, C. A., Wood, L. D., Hebrok, M., Hansen, K., Moses, H. L., & Weaver, V. M.
- Venue
- Nature Medicine
- Published
- 2016-04-18
- Volume
- 22
- Issue
- 5
- Pages
- 497-505
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2337683177
- Cited by
- 603
- References
- 16
- FWCI
- 28.12
- Type
- journal article
- Language
- en
- Open access
- green
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- Laklai, H., Miroshnikova, Y. A., Pickup, M. W., Collisson, E. A., Kim, G. E., Barrett, A. S., Hill, R. C., Lakins, J. N., Schlaepfer, D. D., Mouw, J. K., LeBleu, V. S., Roy, N., Novitskiy, S. V., Johansen, J. S., Poli, V., Kalluri, R., Iacobuzio-Donahue, C. A., Wood, L. D., Hebrok, M., . . . Weaver, V. M. (2016). Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nature Medicine. https://doi.org/10.1038/nm.4082
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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.
