| Literature DB >> 28867147 |
Shizhen Zhu1, Xiaoling Zhang2, Nina Weichert-Leahey3, Zhiwei Dong2, Cheng Zhang4, Gonzalo Lopez5, Ting Tao3, Shuning He3, Andrew C Wood6, Derek Oldridge5, Choong Yong Ung4, Janine H van Ree2, Amish Khan2, Brittany M Salazar2, Edroaldo Lummertz da Rocha4, Mark W Zimmerman3, Feng Guo3, Hong Cao2, Xiaonan Hou7, S John Weroha7, Antonio R Perez-Atayde8, Donna S Neuberg9, Alexander Meves10, Mark A McNiven2, Jan M van Deursen2, Hu Li4, John M Maris11, A Thomas Look12.
Abstract
A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5. Our results provide in vivo validation of LMO1 as an important oncogene that promotes neuroblastoma initiation, progression, and widespread metastatic dissemination.Entities:
Keywords: ECM; LMO1; MYCN; metastasis; neuroblastoma; tumorigenesis; zebrafish model
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Year: 2017 PMID： 28867147 PMCID： PMC5605802 DOI： 10.1016/j.ccell.2017.08.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743