Early Progression Cells mark a stem-like state associated with pancreatic cancer initiation and progression

Early Progression Cells (EPCs) are a stress-adapted, inflammation-responsive cancer stem-like population that is common in early PanIN stages and high-grade progression, but rarer in tumours.

• Why it matters: Many low-grade PanINs exist without cancer risk, so the specific cellular features that mark PanINs that progress are unclear.
• What they did: In a pancreatitis-injury mouse model of pancreatic cancer from rare KrasG12D cells, transcriptomics and EPC protein markers were used to track EPC prevalence across PanIN stages, and sphere/organoid assays tested stem-cell traits and Nupr1 dependence.
• The result: EPCs show stem-cell characteristics in vitro and require Nupr1 stress response pathways for survival and growth; APP-CD74 interaction inhibition in vitro induces high-grade PanIN organoid death, and spatial transcriptomics detects EPC signatures in human PanIN and PDAC regions.

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