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CLCF1–ZIC5–CNTFR feedback loop drives cisplatin resistance in cervical squamous cell carcinoma
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DOI：10.1016/j.neo.2026.101342.png)
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Abstract
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• ZIC5 is upregulated in CDDP-resistant cervical squamous cell carcinoma (CESC) and correlates with poor patient survival. • ZIC5 transcriptionally activates CNTFR, while CLCF1-CNTFR-STAT3 signaling induces ZIC5, forming a positive feedback loop that drives CDDP resistance and cancer stem cell properties. • Blocking CNTFR with a neutralizing antibody disrupts this loop and synergizes with cisplatin to suppress tumor growth in CESC PDX and organoid models.
Keywords:
Cervical squamous cell carcinoma
Cisplatin resistance
CLCF1
ZIC5
CNTFR
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