RUNX2 Recruits the NuRD(MTA1)/CRL4B Complex to Promote Breast Cancer Progression and Bone Metastasis

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2022 May 9

PMID 35534547

Authors

Xin Yin

Xu Teng

Tianyu Ma

Tianshu Yang

Jingyao Zhang

Miaomiao Huo

Wei Liu

Yunkai Yang

Baowen Yuan

Hefen Yu

Wei Huang

Yan Wang

Affiliations

Soon will be listed here.

Abstract

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 (PPARα) 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.

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