AGR2-high cells drive a FOXM1-mediated pro-malignancy program in NF-PanNETs (IMAGE)

Science China Press

AGR2-high cells drive a FOXM1-mediated pro-malignancy program in NF-PanNETs

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Single-cell multi-omics profiling identified an AGR2high endocrine subcluster with malignant features, including increased proliferative activity and enrichment of a metastasis-like primary signature. AGR2 immunohistochemistry further provided clinically informative prognostic stratification in a two-center NF-PanNET cohort. Mechanistically, FOXM1 directly regulated the proliferative transcriptional program of AGR2high cells, while FOXM1 inhibition suppressed tumor growth in tumor cells, patient-derived organoids, and xenograft models.

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