LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis

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

来源：Cancer Cell, 2017, 32(3): 310-+.

DOI：10.1016/j.ccell.2017.08.002

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 dbh 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.

• 出版日期2017-9-11