Promoter Hypermethylation-Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5-Mediated Wnt/β-Catenin Pathway Activation - PubMed
3 days ago
- #Epigenetics
- #Wnt Signaling
- #Breast Cancer
- FXYD1 is identified as a significantly downregulated gene in breast cancer tissues, associated with poor patient prognosis.
- Promoter hypermethylation drives the silencing of FXYD1 in breast cancer.
- Restoration of FXYD1 suppresses cell proliferation, migration, and lung metastasis in vitro and in vivo.
- FXYD1 recruits the E3 ubiquitin ligase MAEA to DDX5, promoting its degradation via K63-linked ubiquitination.
- This process reduces β-catenin stability, impairs its nuclear translocation, and attenuates Wnt target gene expression.
- The study uncovers the FXYD1-MAEA-DDX5 axis as a novel inhibitor of Wnt/β-catenin signaling.
- FXYD1 is proposed as a potential tumor suppressor, prognostic biomarker, and therapeutic target in breast cancer.