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.

doi:10.1101/2022.02.25.481888

bioRxiv · 10.1101/2022.02.25.481888

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.

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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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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. TGF-beta1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer. https://doi.org/10.1101/2022.02.25.481888

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