RUNX2 recruits the NuRD(MTA1)/CRL4B complex to promote breast cancer progression and bone metastasis

Runt-related transcription factor 2 (RUNX2) is an osteogenesis-related transcription factor that has emerged as a prominent transcription repressing factor in carcinogenesis. However, the role of RUNX2 in breast cancer metastasis remains poorly understood. Here, we show that RUNX2 recruits the metastasis-associated 1 (MTA1)/NuRD and the Cullin 4B (CUL4B)-Ring E3 ligase (CRL4B) complex to form a transcriptional-repressive complex, which catalyzes the histone deacetylation and ubiquitylation. Genome-wide analysis of the RUNX2/NuRD(MTA1)/CRL4B complex targets identified a cohort of genes including peroxisome proliferator-activated receptor alpha (PPAR alpha) and superoxide dismutase 2 (SOD2), which are critically involved in cell growth, epithelial-to-mesenchymal transition (EMT) and invasion. We demonstrate that the RUNX2/NuRD(MTA1)/CRL4B complex promotes the proliferation, invasion, tumorigenesis, bone metastasis, cancer stemness of breast cancer in vitro and in vivo. Strikingly, RUNX2 expression is upregulated in multiple human carcinomas, including breast cancer. Our study suggests that RUNX2 is a promising potential target for the future treatment strategies of breast cancer.

Automated summary

RUNX2 has been shown to play an important role in breast cancer metastasis by recruiting the MTA1/NuRD and CRL4B complexes to repress the transcription of key genes involved in cell growth, EMT, and invasion. The RUNX2/NuRD(MTA1)/CRL4B complex promotes breast cancer proliferation, invasion, tumorigenesis, bone metastasis, and cancer stemness both in vitro and in vivo. This study suggests that RUNX2 could be a potential target for future treatment strategies of breast cancer.