The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression
Open accessAbstract
Tissue mechanics regulate development and homeostasis and are consistently modified in tumor progression. Nevertheless, the fundamental molecular mechanisms through which altered mechanics regulate tissue behavior and the clinical relevance of these changes remain unclear. We demonstrate that increased matrix stiffness modulates microRNA expression to drive tumor progression through integrin activation of β-catenin and MYC. Specifically, in human and mouse tissue, increased matrix stiffness induced miR-18a to reduce levels of the tumor suppressor phosphatase and tensin homolog (PTEN), both directly and indirectly by decreasing levels of homeobox A9 (HOXA9). Clinically, extracellular matrix stiffness correlated directly and significantly with miR-18a expression in human breast tumor biopsies. miR-18a expression was highest in basal-like breast cancers in which PTEN and HOXA9 levels were lowest, and high miR-18a expression predicted poor prognosis in patients with luminal breast cancers. Our findings identify a mechanically regulated microRNA circuit that can promote malignancy and suggest potential prognostic roles for HOXA9 and miR-18a levels in stratifying patients with luminal breast cancers.
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Cites
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Self-citationPTEN autoregulates its expression by stabilization of p53 in a phosphatase-independent manner
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Remodelling the extracellular matrix in development and disease
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Emerging Biological Principles of Metastasis
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Force triggers YAP nuclear entry by regulating transport across nuclear pores
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Targeting the tumour stroma to improve cancer therapy
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The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer
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Metadata
- Authors
- Mouw, J. K., Yui, Y., Damiano, L., Bainer, R. O., Lakins, J. N., Acerbi, I., Ou, G., Wijekoon, A. C., Levental, K. R., Gilbert, P. M., Hwang, E. S., Chen, Y.-Y., & Weaver, V. M.
- Venue
- Nature Medicine
- Published
- 2014-03-16
- Volume
- 20
- Issue
- 4
- Pages
- 360-367
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2021597202
- Cited by
- 396
- References
- 6
- FWCI
- 24.09
- Type
- journal article
- Language
- en
- Open access
- green
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- Mouw, J. K., Yui, Y., Damiano, L., Bainer, R. O., Lakins, J. N., Acerbi, I., Ou, G., Wijekoon, A. C., Levental, K. R., Gilbert, P. M., Hwang, E. S., Chen, Y.-Y., & Weaver, V. M. (2014). Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nature Medicine. https://doi.org/10.1038/nm.3497
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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