دورية أكاديمية
HSP90 supports tumor growth and angiogenesis through PRKD2 protein stabilization
| العنوان: | HSP90 supports tumor growth and angiogenesis through PRKD2 protein stabilization |
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| المؤلفون: | Azoitei, Ninel, Diepold, Kristina, Brunner, Cornelia, Rouhi, Arefeh, Genze, Felicitas, Becher, Alexander, Kestler, Hans, Van Lint, Johan, Chiosis, Gabriela, Koren, John, Fröhling, Stefan, Scholl, Claudia, Seufferlein, Thomas |
| بيانات النشر: | Waverly Press |
| سنة النشر: | 2014 |
| المجموعة: | KU Leuven: Lirias |
| مصطلحات موضوعية: | Animals, Apoptosis, Cell Hypoxia, Cell Line, Tumor, Female, HCT116 Cells, HSP90 Heat-Shock Proteins, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Nude, NF-kappa B, Neovascularization, Pathologic, Proteasome Endopeptidase Complex, Protein Kinase C, Signal Transduction, Vascular Endothelial Growth Factor A |
| الوصف: | The kinase PRKD2 (protein kinase D) is a crucial regulator of tumor cell-endothelial cell communication in gastrointestinal tumors and glioblastomas, but its mechanistic contributions to malignant development are not understood. Here, we report that the oncogenic chaperone HSP90 binds to and stabilizes PRKD2 in human cancer cells. Pharmacologic inhibition of HSP90 with structurally divergent small molecules currently in clinical development triggered proteasome-dependent degradation of PRKD2, augmenting apoptosis in human cancer cells of various tissue origins. Conversely, ectopic expression of PRKD2 protected cancer cells from the apoptotic effects of HSP90 abrogation, restoring blood vessel formation in two preclinical models of solid tumors. Mechanistic studies revealed that PRKD2 is essential for hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF1α) and activation of NF-κB in tumor cells. Notably, ectopic expression of PRKD2 was able to partially restore HIF1α and secreted VEGF-A levels in hypoxic cancer cells treated with HSP90 inhibitors. Taken together, our findings indicate that signals from hypoxia and HSP90 pathways are interconnected and funneled by PRKD2 into the NF-κB/VEGF-A signaling axis to promote tumor angiogenesis and tumor growth. ; status: published |
| نوع الوثيقة: | article in journal/newspaper report |
| وصف الملف: | 2553337 bytes; application/pdf |
| اللغة: | English |
| تدمد: | 0008-5472 1538-7445 |
| العلاقة: | Cancer Research vol:74 issue:23 pages:7125-36; https://lirias.kuleuven.be/handle/123456789/492447Test; http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25297628Test; https://lirias.kuleuven.be/bitstream/123456789/492447/1//Hsp90+Azoitei.pdfTest |
| الإتاحة: | https://lirias.kuleuven.be/handle/123456789/492447Test http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25297628Test https://lirias.kuleuven.be/bitstream/123456789/492447/1//Hsp90+Azoitei.pdfTest |
| رقم الانضمام: | edsbas.AE6D581 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00085472 15387445 |
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