LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.

Authors:
Shizhen Zhu
Shizhen Zhu
Dana-Farber Cancer Institute
United States
Xiaoling Zhang
Xiaoling Zhang
Institute of Health Sciences
China
Zhiwei Dong
Zhiwei Dong
Fourth Military Medical University
China
Cheng Zhang
Cheng Zhang
Anhui Medical University
China
Gonzalo Lopez
Gonzalo Lopez
Columbia University
Ting Tao
Ting Tao
Washington University School of Medicine
Shuning He
Shuning He
Institute of Biology

Cancer Cell 2017 09 31;32(3):310-323.e5. Epub 2017 Aug 31.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

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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http://dx.doi.org/10.1016/j.ccell.2017.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605802PMC
September 2017
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