Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells
| العنوان: | Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells |
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| المؤلفون: | Maimon E. Hubbi, Daniele M. Gilkes, Pallavi Chaturvedi, Denis Wirtz, Lisha Xiang, Sun Joo Lee, Gregg L. Semenza |
| المصدر: | Proceedings of the National Academy of Sciences. 111 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Myosin light-chain kinase, RHOA, Cell Survival, Breast Neoplasms, Biology, Focal adhesion, Cell Movement, Cell Line, Tumor, Tumor Microenvironment, Animals, Humans, ROCK1, Neoplasm Metastasis, Phosphorylation, Rho-associated protein kinase, Cytoskeleton, Oligonucleotide Array Sequence Analysis, rho-Associated Kinases, Tumor microenvironment, Microscopy, Confocal, Multidisciplinary, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, Rats, Cell biology, Gene Expression Regulation, Neoplastic, Oxygen, HEK293 Cells, PNAS Plus, Mutation, Cancer cell, Cancer research, biology.protein, Female, Collagen, Signal transduction, rhoA GTP-Binding Protein, Signal Transduction |
| الوصف: | Overexpression of Rho kinase 1 (ROCK1) and the G protein RhoA is implicated in breast cancer progression, but oncogenic mutations are rare, and the molecular mechanisms that underlie increased ROCK1 and RhoA expression have not been determined. RhoA-bound ROCK1 phosphorylates myosin light chain (MLC), which is required for actin-myosin contractility. RhoA also activates focal adhesion kinase (FAK) signaling. Together, these pathways are critical determinants of the motile and invasive phenotype of cancer cells. We report that hypoxia-inducible factors coordinately activate RhoA and ROCK1 expression and signaling in breast cancer cells, leading to cell and matrix contraction, focal adhesion formation, and motility through phosphorylation of MLC and FAK. Thus, intratumoral hypoxia acts as an oncogenic stimulus by triggering hypoxia-inducible factor → RhoA → ROCK1 → MLC → FAK signaling in breast cancer cells. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f06ff566cb590b816faade1382b116c4Test https://doi.org/10.1073/pnas.1321510111Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f06ff566cb590b816faade1382b116c4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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