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The UNC5D-NuRD Repressor Complex Promotes Breast Cancer Progression by Negatively Regulating GSK3B

ABSTRACT: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for UNC5D in MDA-MB-231 cells. UNC5D serves as a receptor for Netrin-1 and is highly expressed in breast cancer. Here, we report that UnICD, generated by caspase cleavage of UNC5D, translocates to the nucleus, interacts with the NuRD complex, and promotes tumorigenesis and development by relieving or reducing its suppression of β-catenin through inhibiting the transcription of GSK3B. In vitro experiments showed that the knockdown of UNC5D can inhibit the proliferation of breast cancer cells. Consistently, the expression level of UNC5D in breast cancer was negatively correlated with the expression level of GSK3B, and high levels of UNC5D were associated with poor prognosis in breast cancer patients. These results suggest that UNC5D is a pivotal driver in breast carcinogenesis, potentially inducing the initiation and progression of breast cancer through the UnICD/NuRD-GSK3B-β-catenin axis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269850 | GEO | 2025/06/14

REPOSITORIES: GEO

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