@article{98107554f4c54450b8b380a92048816e,
title = "LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis",
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. High expression of LMO1 is associated with neuroblastoma (NB) metastases. Zhu et al. show that LMO1 synergizes with MYCN to promote NB development and metastasis in zebrafish and that LMO1 elevates expression of genes affecting tumor cell-extracellular matrix interaction and promotes NB cell invasion.",
keywords = "ECM, LMO1, MYCN, metastasis, neuroblastoma, tumorigenesis, zebrafish model",
author = "Shizhen Zhu and Xiaoling Zhang and Nina Weichert-Leahey and Zhiwei Dong and Cheng Zhang and Gonzalo Lopez and Ting Tao and Shuning He and Wood, {Andrew C.} and Derek Oldridge and Ung, {Choong Yong} and {van Ree}, {Janine H.} and Amish Khan and Salazar, {Brittany M.} and {Lummertz da Rocha}, Edroaldo and Zimmerman, {Mark W.} and Feng Guo and Hong Cao and Xiaonan Hou and Weroha, {S. John} and Perez-Atayde, {Antonio R.} and Neuberg, {Donna S.} and Alexander Meves and McNiven, {Mark A.} and {van Deursen}, {Jan M.} and Hu Li and Maris, {John M.} and Look, {A. Thomas}",
note = "Funding Information: We thank J.R. Gilbert for editorial review of the manuscript and critical comments. This work was supported by a grant R00CA178189 (S.Z.) from the National Cancer Institute ; a grant W81XWH-17-1-0498 (S.Z.) from the United States Department of Defense (DoD); young investigator awards from the Alex's Lemonade Stand Foundation (S.Z.) and the CureSearch for Children's Cancer Foundation (S.Z.); a V Scholar award from the V Foundation for Cancer Research (S.Z.) and pilot project awards from the Fraternal Order of Eagles (S.Z.) and the Mayo Center for Biomedical Discovery (S.Z.); support from the Mayo Clinic Cancer Center , Center for Biomedical Discovery , and Center for Individualized Medicine (S.Z.); a grant R01 CA180692 (J.M.M. and A.T.L.) from the National Cancer Institute; an Alex's Lemonade Stand Foundation Innovation Award (A.T.L.); a grant R01 CA124709 from the National Cancer Institute and an award from the Press On Foundation (J.M.M.); a grant R01 CA196631-01A1 (H.L.) from the National Institutes of Health ; a fellowship from the Friends for Life and the Friends of DFCI, a grant from the Children's Neuroblastoma Cancer Foundation (T.T.); a grant from the German Cancer Aid 110801 (N.W.-L.); a fellowship from the Damon Runyon-Sohn Foundation (DRSG-9-14) (M.W.Z.). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = sep,
day = "11",
doi = "10.1016/j.ccell.2017.08.002",
language = "English (US)",
volume = "32",
pages = "310--323.e5",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}