LMO1 synergizes with MYCN to promote neuroblastoma initiation and metastasis

Authors: Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Zhiwei Dong, Cheng Zhang, Gonzalo Lopez, Ting Tao, Shuning He, Andrew C. Wood, Derek Oldridge, Choong Yong Ung, Janine H. van Ree, Amish Khan, Brittany M. Salazar, Edroaldo Lummertz da Rocha, Mark W. Zimmerman, Feng Guo, Hong Cao, Xiaonan Hou, S. John Weroha, Antonio R. Perez-Atayde, Donna S. Neuberg, Alexander Meves, Mark A. McNiven, Jan M. van Deursen, Hu Li, John M. Maris, A. Thomas Look


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.

Source: Cancer Cell; 2017