The histone demethylase KDM4A promotes esophageal cancer progression by epigenetically activating LRG1-mediated TGF-β signaling - PubMed
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- #ESCC
- #KDM4A
- #Epigenetics
- KDM4A is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and correlates with poor prognosis.
- KDM4A promotes ESCC cell proliferation, migration, invasion, and tumor growth both in vitro and in vivo.
- Mechanistically, KDM4A demethylates H3K9me3 at the LRG1 promoter, enhancing LRG1 transcription and activating the TGF-β pathway.
- Activation of the TGF-β pathway drives epithelial-mesenchymal transition (EMT) and cancer stemness in ESCC.
- Knockdown of KDM4A or LRG1 suppresses oncogenic phenotypes, while LRG1 overexpression rescues KDM4A deficiency-induced impairments.
- KDM4A and LRG1 are co-overexpressed in ESCC tissues and associated with advanced tumor stage and shorter overall survival.
- The KDM4A-LRG1-TGF-β axis is identified as a critical driver of ESCC progression and a potential therapeutic target.