LMO1 enhances casein kinase 2 activity to promote MYCN expression in neuroblastoma

Abstract Neuroblastoma (NB) is the most common extracranial solid tumor in children, accounting for ~ 15% of pediatric cancer-related mortality. Despite intensive multimodal therapy, high-risk NB survival remains below 50%. LIM-domain-only 1 (LMO1) has been identified as a key NB predisposition gene, with elevated expression strongly associated with advanced disease stage and metastasis. However, the molecular mechanisms underlying its oncogenic function remain incompletely defined. Here, using mass spectrometry-based analysis of proteins immunoprecipitated with LMO1, we identified CSNK2B, the regulatory β subunit of casein kinase 2 (CK2), as a previously unrecognized LMO1-interacting proteins. We demonstrated that LMO1 is associated with increased phosphorylation of CSNK2B at serine 209 (Ser209), and that phosphorylated CSNK2B correlates with increased CK2 activity and advanced NB stages. Mechanistically, chromatin immunoprecipitation-qPCR analyses revealed that LMO1 overexpression enhances BRD4 occupancy at the MYCN promoter, linking the LMO1-CSNK2B-CK2 signaling to transcriptional activation of MYCN. Collectively, these findings uncover a previously unrecognized LMO1-CSNK2B-CK2-BRD4-MYCN signaling axis that contribute to NB tumorigenesis and provide new insight into LMO1-mediated oncogenic signaling in high-risk NB.