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TGF-beta1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer

Low, R. R. J.; Fung, K. Y.; Gao, H.; Preaudet, A.; Dagley, L. F.; Yousef, J.; Lee, B.; Larsen, R. H.; Kershaw, N. J.; Burgess, A. W.; Gibbs, P.; Hollande, F.; Griffin, M. D. W.; Grimmond, S. M.; Putoczki, T. L.

2022-02-26 cancer biology
10.1101/2022.02.25.481888 bioRxiv
Show abstract

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 proteomics approach, we found that the morphology of the organoids predicts the EMT state, with solid organoids associated with a P-EMT signature. We also observed that exogenous TGF{beta}1 induces a solid organoid morphology that is associated with changes in the S100 family, C-EMT and the formation of high-grade tumors. S100A4 may represent a useful biomarker to predict EMT state, disease progression and outcome for pancreatic cancer patients.

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