Keratin 17 Defines an Epithelial-Mesenchymal Transition-Associated Migratory Cell State in Pancreatic Ductal Adenocarcinoma

K17-positive malignant epithelial cells in pancreatic ductal adenocarcinoma are enriched for EMT-associated programs, and K17/LAMC2 double-positive tumors show worse overall survival (adjusted HR = 2.53).

• Why it matters: K17 marks an aggressive basal-like PDAC subtype and predicts adverse prognosis, but the cellular programs and mechanisms linking K17 to invasion and resistance were unclear.
• What they did: Integrated scRNA-seq from 42 patients, CPTAC proteomics from 140 tumors, MACSima spatial imaging of 63 patients, dual-plex IHC of 60 cases, and 3D spheroid migration assays; LAMC2 was the only K17-associated candidate across validation steps.
• The result: Spatial and IHC analyses localized K17 to poorly differentiated regions with frequent single-cell K17/LAMC2 co-expression and increasing enrichment with histologic grade; functional gain/loss-of-function in 3D spheroids showed K17 promotes migratory outgrowth without proliferation differences.