PUBLICATION
LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis
- Authors
- 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.
- ID
- ZDB-PUB-170905-9
- 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
-
- Extracellular Matrix/metabolism
- N-Myc Proto-Oncogene Protein/metabolism*
- Cell Movement/genetics
- DNA-Binding Proteins/metabolism*
- Neuroblastoma/genetics
- Neuroblastoma/metabolism*
- Neuroblastoma/pathology*
- Transgenes
- Transcription Factors/metabolism*
- Neoplasm Invasiveness
- Models, Biological
- Zebrafish
- Hyperplasia
- Signal Transduction/genetics
- Cell Line, Tumor
- Neoplasm Metastasis
- Animals
- Gene Expression Regulation, Neoplastic
- Carcinogenesis/metabolism
- Carcinogenesis/pathology*
- Humans
- Animals, Genetically Modified
- LIM Domain Proteins/metabolism*
- PubMed
- 28867147 Full text @ Cancer Cell
Citation
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. (2017) LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis. Cancer Cell. 32(3):310-323.e5.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping