STN1 facilitates metastasis by promoting transcription of EMT-activator ZEB1 in pancreatic cancer
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ABSTRACT: As pancreatic ductal adenocarcinoma (PDAC) poses a formidable clinical challenge, demanding further exploration of its pathogenesis and drugs targeted for metastasis-the main cause of mortality. Here, we identified STN1, a CST complex member crucial for maintaining telomere lengths and genome stability, as a key factor in promoting PDAC metastasis. Elevated STN1 levels correlate with poor patient survival, with oncogenic protein HOXB7 as an upstream transcription factor regulating STN1. Utilizing multiple PDAC experimental models, we discovered STN1’s role in promoting metastasis by acting as a novel upstream factor in epithelial-mesenchymal transition (EMT). Mechanistically, our proposed model suggests that during transcription, STN1 binds to displaced single-stranded DNA adjacent to the R-loop, recruiting STAT3 to activate ZEB1 transcription independent of its known telomere maintenance function. Notably, STAT3 inhibitors show enhanced efficiency in restraining metastatic potential in STN1-overexpressed PDAC cells, offering promise as a therapeutic avenue for targeting metastasis in STN1-overexpressed PDAC patients facing an unfavorable prognosis.
ORGANISM(S): Homo sapiens
PROVIDER: GSE282970 | GEO | 2025/05/18
REPOSITORIES: GEO
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