ZFIN ID: ZDB-PUB-170905-9
LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis
Zhu, S., Zhang, X., Weichert-Leahey, N., Dong, Z., Zhang, C., Lopez, G., Tao, T., He, S., Wood, A.C., Oldridge, D., Ung, C.Y., van Ree, J.H., Khan, A., Salazar, B.M., Lummertz da Rocha, E., Zimmerman, M.W., Guo, F., Cao, H., Hou, X., Weroha, S.J., Perez-Atayde, A.R., Neuberg, D.S., Meves, A., McNiven, M.A., van Deursen, J.M., Li, H., Maris, J.M., Look, A.T.
Date: 2017
Source: Cancer Cell   32(3): 310-323.e5 (Journal)
Registered Authors: Dong, Zhiwei, He, Shuning, Look, A. Thomas, Tao, Ting, Zhang, Xiaoling, Zhu, Shizhen, Zimmerman, Mark
Keywords: ECM, LMO1, MYCN, metastasis, neuroblastoma, tumorigenesis, zebrafish model
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Carcinogenesis/metabolism
  • Carcinogenesis/pathology*
  • Cell Line, Tumor
  • Cell Movement/genetics
  • DNA-Binding Proteins/metabolism*
  • Extracellular Matrix/metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperplasia
  • LIM Domain Proteins/metabolism*
  • Models, Biological
  • N-Myc Proto-Oncogene Protein/metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neuroblastoma/genetics
  • Neuroblastoma/metabolism*
  • Neuroblastoma/pathology*
  • Signal Transduction/genetics
  • Transcription Factors/metabolism*
  • Transgenes
  • Zebrafish
PubMed: 28867147 Full text @ Cancer Cell
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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.
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