The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Tissue mechanics promote IDH1-dependent HIF1α–tenascin C feedback to regulate glioblastoma aggression
Open accessAbstract
Increased overall survival for patients with glioma brain tumours is associated with mutations in the metabolic regulator isocitrate dehydrogenase 1 (IDH1). Gliomas develop within a mechanically challenged microenvironment that is characterized by a dense extracellular matrix (ECM) that compromises vascular integrity to induce hypoxia and activate HIF1α. We found that glioma aggression and patient prognosis correlate with HIF1α levels and the stiffness of a tenascin C (TNC)-enriched ECM. Gain- and loss-of-function xenograft manipulations demonstrated that a mutant IDH1 restricts glioma aggression by reducing HIF1α-dependent TNC expression to decrease ECM stiffness and mechanosignalling. Recurrent IDH1-mutant patient gliomas had a stiffer TNC-enriched ECM that our studies attributed to reduced miR-203 suppression of HIF1α and TNC mediated via a tension-dependent positive feedback loop. Thus, our work suggests that elevated ECM stiffness can independently foster glioblastoma aggression and contribute to glioblastoma recurrence via bypassing the protective activity of IDH1 mutational status.
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Cites
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“To examine the relationship between IDH mutation and ECM stiffness, we used a candidate approach to profile major ECM constituents in GBM, hyaluronic acid (HA), and HA-interacting molecules 14,15 .”
Cited by
Nia, H. T., Munn, L. L., & Jain, R. K. (2020) · Science · doi:10.1126/science.aaz0868 · Cited by 855
Chen, Y., Kim, J., Yang, S., Wang, H., Wu, C.-J., Sugimoto, H., LeBleu, V. S., & Kalluri, R. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.02.007 · Cited by 566
Glioblastoma stem cells: lessons from the tumor hierarchy in a lethal cancer
Gimple, R. C., Bhargava, S., Dixit, D., & Rich, J. N. (2019) · Genes & Development · doi:10.1101/gad.324301.119 · Cited by 514
Midwood, K. S., Chiquet, M., Tucker, R. P., & Orend, G. (2016) · Journal of Cell Science · doi:10.1242/jcs.190546 · Cited by 429
Metadata
- Authors
- Miroshnikova, Y. A., Mouw, J. K., Barnes, J. M., Pickup, M. W., Lakins, J. N., Kim, Y., Lobo, K., Persson, A. I., Reis, G. F., McKnight, T. R., Holland, E. C., Phillips, J. J., & Weaver, V. M.
- Venue
- Nature Cell Biology
- Published
- 2016-11-07
- Volume
- 18
- Issue
- 12
- Pages
- 1336-1345
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2555999948
- Cited by
- 383
- References
- 15
- FWCI
- 14.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Miroshnikova, Y. A., Mouw, J. K., Barnes, J. M., Pickup, M. W., Lakins, J. N., Kim, Y., Lobo, K., Persson, A. I., Reis, G. F., McKnight, T. R., Holland, E. C., Phillips, J. J., & Weaver, V. M. (2016). Tissue mechanics promote IDH1-dependent HIF1α–tenascin C feedback to regulate glioblastoma aggression. Nature Cell Biology. https://doi.org/10.1038/ncb3429
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