کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456823 | 1548777 | 2018 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
EGFBMP4RNAseqqRT-PCRERKCyclin D1CCND1PBSRspo2EPAS1atRA - ATRAMAPK - MAPKTCF/LEF - TCF / LEFALK - آلکall-trans-retinoic acid - اسید کلرید رتینوئیکSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدRNA sequencing - ترتیب RNAEMT - تکنسین فوریتهای پزشکیKEGG یا Kyoto Encyclopedia of Genes and Genomes - دایرة المعارف ژن ها و ژنوم کیوتو Kyoto Encyclopedia of Genes and Genomes - دایره المعارف ژنتیک ژن ها و ژنوم کیوتوretinoblastoma - رتینوبلاستوما، تومور شبکیهepidermal growth factor - عامل رشد اپیدرمیAnaplastic lymphoma kinase - لنفوم کیناز AnaplasticMEK - مجاهدین خلقPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریQuantitative reverse-transcriptase polymerase chain reaction - واکنش زنجیره ای پلیمراز معکوس ترانس کریتازbone morphogenetic protein 4 - پروتئین مورفوژنیک استخوان 4mitogen-activated protein kinase - پروتئین کیناز فعال با mitogenmitogen-activated protein kinase kinase - پروتئین کیناز کیناز فعال Mitogen فعالextracellular signal-regulated kinases - کیناز های تنظیم شده سیگنال خارج سلولیEpithelial-mesenchymal transition - گذار اپیتلیال-مزانشیمی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Neuroblastoma is one of the commonest and deadliest solid tumours of childhood, and is thought to result from disrupted differentiation of the developing sympathoadrenergic lineage of the neural crest. Neuroblastoma exhibits intra- and intertumoural heterogeneity, with high risk tumours characterised by poor differentiation, which can be attributable to MYCN-mediated repression of genes involved in neuronal differentiation. MYCN is known to co-operate with oncogenic signalling pathways such as Alk, Akt and MEK/ERK signalling, and, together with c-MYC has been shown to be activated by Wnt signalling in various tissues. However, our previous work demonstrated that Wnt3a/Rspo2 treatment of some neuroblastoma cell lines can, paradoxically, decrease c-MYC and MYCN proteins. This prompted us to define the neuroblastoma-specific Wnt3a/Rspo2-driven transcriptome using RNA sequencing, and characterise the accompanying changes in cell biology. Here we report the identification of ninety Wnt target genes, and show that Wnt signalling is upstream of numerous transcription factors and signalling pathways in neuroblastoma. Using live-cell imaging, we show that Wnt signalling can drive differentiation of SK-N-BE(2)-C and SH-SY5Y cell-lines, but, conversely, proliferation of SK-N-AS cells. We show that cell-lines that differentiate show induction of pro-differentiation BMP4 and EPAS1 proteins, which is not apparent in the SK-N-AS cells. In contrast, SK-N-AS cells show increased CCND1, phosphorylated RB and E2F1 in response to Wnt3a/Rspo2, consistent with their proliferative response, and these proteins are not increased in differentiating lines. By meta-analysis of the expression of our 90 genes in primary tumour gene expression databases, we demonstrate discrete expression patterns of our Wnt genes in patient cohorts with different prognosis. Furthermore our analysis reveals interconnectivity within subsets of our Wnt genes, with one subset comprised of novel putative drivers of neuronal differentiation repressed by MYCN. Assessment of β-catenin immunohistochemistry shows high levels of β-catenin in tumours with better differentiation, further supporting a role for canonical Wnt signalling in neuroblastoma differentiation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 20, Issue 4, April 2018, Pages 335-350
Journal: Neoplasia - Volume 20, Issue 4, April 2018, Pages 335-350
نویسندگان
Marianna Szemes, Alexander Greenhough, Zsombor Melegh, Sally Malik, Aysen Yuksel, Daniel Catchpoole, Kelli Gallacher, Madhu Kollareddy, Ji Hyun Park, Karim Malik,