The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC.
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Cites
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Cited by
Targeting the tumour stroma to improve cancer therapy
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Role of Extracellular Matrix in Development and Cancer Progression
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Self-citationPancreatic cancer stroma: an update on therapeutic targeting strategies
Hosein, A. N., Brekken, R. A., & Maitra, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0300-1 · Cited by 950
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
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The role of collagen in cancer: from bench to bedside
Xu, S., Xu, H., Wang, W., Li, S., Li, H., Li, T., Zhang, W., Yu, X., & Liu, L. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-2058-1 · Cited by 735
Metadata
- Authors
- Chronopoulos, A., Robinson, B., Sarper, M., Cortes, E., Auernheimer, V., Lachowski, D., Attwood, S., García, R., Ghassemi, S., Fabry, B., & del Río Hernández, A.
- Venue
- Nature Communications
- Published
- 2016-09-07
- Volume
- 7
- Issue
- 1
- Pages
- 12630-12630
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2510391033
- Cited by
- 274
- References
- 9
- FWCI
- 14.86
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chronopoulos, A., Robinson, B., Sarper, M., Cortes, E., Auernheimer, V., Lachowski, D., Attwood, S., García, R., Ghassemi, S., Fabry, B., & del Río Hernández, A. (2016). ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion. Nature Communications. https://doi.org/10.1038/ncomms12630
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