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DOI | 10.1038/s41586-020-1996-3 |
Loss of p53 drives neuron reprogramming in head and neck cancer | |
Lipson, Mark1; 39;ane2 | |
2020-01-30 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2020 |
卷号 | 578期号:7795页码:449-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Japan; Norway |
英文关键词 | MicroRNAs from head and neck cancer cells, shuttled to sensory neurons by extracellular vesicles, cause a shift to an adrenergic neuronal phenotype that promotes tumour progression. The solid tumour microenvironment includes nerve fibres that arise from the peripheral nervous system(1,2). Recent work indicates that newly formed adrenergic nerve fibres promote tumour growth, but the origin of these nerves and the mechanism of their inception are unknown(1,3). Here, by comparing the transcriptomes of cancer-associated trigeminal sensory neurons with those of endogenous neurons in mouse models of oral cancer, we identified an adrenergic differentiation signature. We show that loss of TP53 leads to adrenergic transdifferentiation of tumour-associated sensory nerves through loss of the microRNA miR-34a. Tumour growth was inhibited by sensory denervation or pharmacological blockade of adrenergic receptors, but not by chemical sympathectomy of pre-existing adrenergic nerves. A retrospective analysis of samples from oral cancer revealed that p53 status was associated with nerve density, which was in turn associated with poor clinical outcomes. This crosstalk between cancer cells and neurons represents mechanism by which tumour-associated neurons are reprogrammed towards an adrenergic phenotype that can stimulate tumour progression, and is a potential target for anticancer therapy. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000513111200009 |
WOS关键词 | MICRORNA TARGET PREDICTION ; GAIN-OF-FUNCTION ; EXTRACELLULAR VESICLES ; PERINEURAL INVASION ; MOUSE MODEL ; FIBROBLASTS ; EXPRESSION ; IDENTIFICATION ; CARCINOMA ; RESOURCE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281405 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA; 2.Univ Montreal, Dept Anthropol, Montreal, PQ, Canada; 3.Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA; 4.Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA; 5.UCL, UCL Genet Inst, London, England; 6.Univ Yaounde I, Dept Arts & Archaeol, Yaounde, Cameroon; 7.Univ Tubingen, Dept Geosci, Biogeol, Tubingen, Germany; 8.Univ Tubingen, Senckenberg Res Ctr Human Evolut & Palaeoenvironm, Tubingen, Germany; 9.Penn State Univ, Inst Energy & Environm, University Pk, PA 16802 USA; 10.Royal Museum Cent Africa, Dept Cultural Anthropol & Hist, Tervuren, Belgium; 11.Univ Bordeaux, CNRS, UMR 5199, PACEA, Bordeaux, France; 12.Univ Libre Bruxelles, Fac Philosophie & Sci Sociales, Brussels, Belgium; 13.Univ Buea, Dept Hist & African Civilizat, Buea, Cameroon; 14.Agence Wallonne Patrimoine, Serv Publ Wallonie, Namur, Belgium; 15.Royal Belgian Inst Nat Sci, Brussels, Belgium; 16.SUNY Stony Brook, Dept Anthropol, Stony Brook, NY 11794 USA; 17.UCL, Dept Genet Evolut & Environm, London, England; 18.Univ Leuven, Dept Biol, Leuven, Belgium; 19.SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA; 20.Univ Calif Santa Barbara, Dept Anthropol, Santa Barbara, CA 93106 USA; 21.Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA; 22.UPF, CSIC, Inst Evolutionary Biol, Barcelona, Spain; 23.Duke Kunshan Univ, Div Social Sci, Kunshan, Peoples R China; 24.St Louis Univ, Dept Sociol & Anthropol, Madrid, Spain; 25.Univ Calif Santa Cruz, Dept Anthropol, Santa Cruz, CA 95064 USA; 26.Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA; 27.Henry Stewart Grp, London, England |
推荐引用方式 GB/T 7714 | Lipson, Mark,39;ane. Loss of p53 drives neuron reprogramming in head and neck cancer[J]. NATURE,2020,578(7795):449-+. |
APA | Lipson, Mark,&39;ane.(2020).Loss of p53 drives neuron reprogramming in head and neck cancer.NATURE,578(7795),449-+. |
MLA | Lipson, Mark,et al."Loss of p53 drives neuron reprogramming in head and neck cancer".NATURE 578.7795(2020):449-+. |
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