STAT3-mediated transactivation of NOVA2 promotes lung adenocarcinoma metastasis by splicing SMAD4 - PubMed
4 hours ago
- #lung adenocarcinoma
- #STAT3 signaling
- #RNA splicing
- NOVA2, an RNA-binding protein, is identified as a key regulator in lung adenocarcinoma (LUAD) metastasis, with high expression linked to poor prognosis.
- STAT3, facilitated by p300-mediated H3K27 acetylation, transactivates NOVA2 transcription, increasing its expression.
- Elevated NOVA2 causes exon skipping (exons 6-7) in SMAD4, producing a truncated Δ-SMAD4 isoform resistant to β-TrCP-mediated ubiquitination.
- Δ-SMAD4 maintains TGF-β/SMAD signaling by forming complexes with SMAD3, promoting epithelial-mesenchymal transition (EMT) and metastasis in LUAD.
- Targeting the STAT3-NOVA2-Δ-SMAD4 axis may offer therapeutic potential for inhibiting LUAD metastasis.