S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer
Ronnie Ren Jie Low, Ka Yee Fung, Hugh Gao, Adele Preaudet, Laura F. Dagley, Jumana Yousef, Belinda Lee, Samantha J. Emery‐Corbin, Paul M. Nguyen, Rune H. Larsen, Nadia J. Kershaw, Antony W. Burgess, Peter Gibbs, Frédéric Hollande, Michael D. W. Griffin, Sean M. Grimmond, Tracy L. Putoczki
Abstract
Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT, and mesenchymal states, each of which is associated with cancer progression, invasive capabilities, and ultimately, metastasis. We used a lineage-traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that underwent partial EMT and complete EMT. Using an unbiased proteomics approach, we found that organoid morphology predicts the EMT state, and the solid organoids are associated with a partial EMT signature. We also observed that exogenous TGFβ1 induces solid organoid morphology that is associated with changes in the S100 family, complete EMT, and the formation of high-grade tumors. S100A4 may be a useful biomarker for predicting EMT state, disease progression, and outcome in patients with pancreatic cancer.