The collagen prolyl hydroxylases are bifunctional growth regulators in melanoma
| العنوان: | The collagen prolyl hydroxylases are bifunctional growth regulators in melanoma |
|---|---|
| المؤلفون: | Alan Evans, L. Weir, Aithne Atkinson, Colin Fleming, Tim Crook, Alexander Renziehausen, Rubeta Matin, J. Geoffrey Pickering, Su Li, Peter W. Szlosarek, Laura Lattanzio, Ronald T. Raines, Marco Merlano, Van Ren Sim, Alastair M. Thompson, Hexiao Wang, James T. Vasta, Catherine A. Harwood, Cristiana Lo Nigro, Charlotte M. Proby, Mathieu Boniol, Nelofer Syed, Bhavya Rao |
| المساهمون: | Brain Tumour Research Campaign, Massachusetts Institute of Technology. Department of Chemistry |
| المصدر: | J Invest Dermatol Other repository |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Skin Neoplasms, Biochemistry, Hydroxylation, chemistry.chemical_compound, 0302 clinical medicine, Reference Values, Transcriptional regulation, Melanoma, Regulation of gene expression, Prolyl hydroxylases, Chemistry, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, SURVIVAL, biomarker, Collagen, Life Sciences & Biomedicine, EXPRESSION, Procollagen-Proline Dioxygenase, INHIBITION, Dermatology, MOUSE GENES, Article, 03 medical and health sciences, Cell Line, Tumor, medicine, Gene silencing, Humans, 1112 Oncology and Carcinogenesis, Epigenetics, Molecular Biology, Cell Proliferation, Science & Technology, epigenetics, Dermatology & Venereal Diseases, 4-HYDROXYLASE, 1103 Clinical Sciences, Cell Biology, DNA Methylation, medicine.disease, 030104 developmental biology, Cell culture, SUBUNIT, Cancer research, Ectopic expression, methylation, Protein Processing, Post-Translational |
| الوصف: | Appropriate post-translational processing of collagen requires prolyl hydroxylation, catalyzed by collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase, and is essential for normal cell function. Here we have investigated the expression, transcriptional regulation, and function of the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families in melanoma. We show that the collagen prolyl 3-hydroxylase family exemplified by Leprel1 and Leprel2 is subject to methylation-dependent transcriptional silencing in primary and metastatic melanoma consistent with a tumor suppressor function. In contrast, although there is transcriptional silencing of P4HA3 in a subset of melanomas, the collagen prolyl 4-hydroxylase family members P4HA1, P4HA2, and P4HA3 are often overexpressed in melanoma, expression being prognostic of worse clinical outcomes. Consistent with tumor suppressor function, ectopic expression of Leprel1 and Leprel2 inhibits melanoma proliferation, whereas P4HA2 and P4HA3 increase proliferation, and particularly invasiveness, of melanoma cells. Pharmacological inhibition with multiple selective collagen prolyl 4-hydroxylase inhibitors reduces proliferation and inhibits invasiveness of melanoma cells. Together, our data identify the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families as potentially important regulators of melanoma growth and invasiveness and suggest that selective inhibition of collagen prolyl 4-hydroxylase is an attractive strategy to reduce the invasive properties of melanoma cells. National Institute of Health (U.S.) (Grant R01 AR044276) |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b3351c8f939c7481a5da5b730022427 http://hdl.handle.net/10044/1/65729 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0b3351c8f939c7481a5da5b730022427 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |