دورية أكاديمية
Hypoxia promotes breast cancer cell invasion through HIF-1a-mediated up-regulation of the invadopodial actin bundling protein CSRP2
| العنوان: | Hypoxia promotes breast cancer cell invasion through HIF-1a-mediated up-regulation of the invadopodial actin bundling protein CSRP2 |
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| المؤلفون: | Hoffmann, C, Mao, X, Brown-Clay, J, Moreau, F, Al Absi, A, Wurzer, H, Sousa, B, Schmitt, F, Berchem, G, Janji, B, Thomas, C |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2018 |
| المجموعة: | Repositório Aberto da Universidade do Porto |
| مصطلحات موضوعية: | Adult, Aged, Animals, Breast / pathology, Breast Neoplasms / genetics, Breast Neoplasms / mortality, Breast Neoplasms / pathology, Cell Hypoxia, Cell Line, Tumor, Cell Movement, Extracellular Matrix / pathology, Female, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Hypoxia-Inducible Factor 1, alpha Subunit / genetics, alpha Subunit / metabolism, Kaplan-Meier Estimate, LIM Domain Proteins / genetics, LIM Domain Proteins / metabolism, Mice, Middle Aged, Muscle Proteins / genetics, Muscle Proteins / metabolismo, Neoplasm Invasiveness / pathology, Nuclear Proteins / genetics, Nuclear Proteins / metabolismo |
| الوصف: | Hypoxia is a common feature of solid tumours that promotes invasion and metastatic dissemination. Invadopodia are actin-rich membrane protrusions that direct extracellular matrix proteolysis and facilitate tumour cell invasion. Here, we show that CSRP2, an invadopodial actin bundling protein, is upregulated by hypoxia in various breast cancer cell lines, as well as in pre-clinical and clinical breast tumour specimens. We functionally characterized two hypoxia responsive elements within the proximal promoter of CSRP2 gene which are targeted by hypoxia-inducible factor-1 (HIF-1) and required for promoter transactivation in response to hypoxia. Remarkably, CSRP2 knockdown significantly inhibits hypoxia-stimulated invadopodium formation, ECM degradation and invasion in MDA-MB-231 cells, while CSRP2 forced expression was sufficient to enhance the invasive capacity of HIF-1a-depleted cells under hypoxia. In MCF-7 cells, CSRP2 upregulation was required for hypoxia-induced formation of invadopodium precursors that were unable to promote ECM degradation. Collectively, our data support that CSRP2 is a novel and direct cytoskeletal target of HIF-1 which facilitates hypoxia-induced breast cancer cell invasion by promoting invadopodia formation. ; The authors are grateful to Monika Dieterle, Arnaud Muller, Pter Nazarov and Muhammad Zaeem Noman (Oncology Department, LIH, Luxembourg) for technical assistance, support in statistical analyses and constructive discussions. The authors also warmly thank Sara A. Courtneidge for the gift of the Tks5-GFP construct (Oregon Health and Science University, Portland, USA). This work was mainly supported by a research grant from “Fondation Cancer” Luxembourg (FC/2016/02), and the National Research Fund (C16/ BM/11297905). Joshua Brown Clay is recipient of a Postdoctoral fellowship from “Fonds De La Recherche Scientifque” - FNRS “Télévie” (7.4512.16). Antoun Al Absi and Hannah Wurzer are recipients of PhD fellowships from the National Research Fund, Luxembourg (AFR7892325 and ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | Scientific Reports, vol.8(1):10191; https://www.nature.com/articles/s41598-018-28637-xTest; https://hdl.handle.net/10216/127417Test |
| DOI: | 10.1038/s41598-018-28637-x |
| الإتاحة: | https://doi.org/10.1038/s41598-018-28637-xTest https://hdl.handle.net/10216/127417Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.80BC3768 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-018-28637-x |