TGFB1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer

Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT (P-EMT) and mesenchymal states, each of which are associated with cancer progression, invasive capabilities and ultimately metastasis. We have employed a lineage traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that have undergone P-EMT and complete EMT (C-EMT). Using an unbiased quantitative proteomics approach, we found that the morphology of the organoids could predict EMT state, with solid organoids associated with a C-EMT signature. We also observed that exogenous TGFb1 could induce a solid organoid morphology that was associated with changes in the S100 family of proteins and the formation of high-grade tumors. Our work reveals that S100A4 may represent a useful biomarker to predict EMT state, disease progression and outcome.