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TGF-β1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer

View ORCID ProfileRonnie Ren Jie Low, Ka Yee Fung, Hugh Gao, Adele Preaudet, Laura F. Dagley, Jumana Yousef, Belinda Lee, Rune H. Larsen, Nadia J. Kershaw, Antony W. Burgess, Peter Gibbs, Frédéric Hollande, Michael D.W. Griffin, Sean M. Grimmond, Tracy L. Putoczki
doi: https://doi.org/10.1101/2022.02.25.481888
Ronnie Ren Jie Low
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
3University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, Victoria 3000, Australia
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  • ORCID record for Ronnie Ren Jie Low
Ka Yee Fung
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Hugh Gao
3University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, Victoria 3000, Australia
4Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria 3000, Australia
5Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia
6Department of Molecular and Translational Science, Monash University, Clayton, VIC 3800, Australia
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Adele Preaudet
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Laura F. Dagley
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Jumana Yousef
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Belinda Lee
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Rune H. Larsen
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Nadia J. Kershaw
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Antony W. Burgess
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Peter Gibbs
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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Frédéric Hollande
3University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, Victoria 3000, Australia
4Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria 3000, Australia
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Michael D.W. Griffin
7Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, 3000, Australia
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Sean M. Grimmond
3University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, Victoria 3000, Australia
4Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria 3000, Australia
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Tracy L. Putoczki
1The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052
2Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052
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  • For correspondence: putoczki.t@wehi.edu.au
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SUMMARY

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 TGFβ1 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 26, 2022.
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TGF-β1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer
Ronnie Ren Jie Low, Ka Yee Fung, Hugh Gao, Adele Preaudet, Laura F. Dagley, Jumana Yousef, Belinda Lee, Rune H. Larsen, Nadia J. Kershaw, Antony W. Burgess, Peter Gibbs, Frédéric Hollande, Michael D.W. Griffin, Sean M. Grimmond, Tracy L. Putoczki
bioRxiv 2022.02.25.481888; doi: https://doi.org/10.1101/2022.02.25.481888
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TGF-β1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer
Ronnie Ren Jie Low, Ka Yee Fung, Hugh Gao, Adele Preaudet, Laura F. Dagley, Jumana Yousef, Belinda Lee, Rune H. Larsen, Nadia J. Kershaw, Antony W. Burgess, Peter Gibbs, Frédéric Hollande, Michael D.W. Griffin, Sean M. Grimmond, Tracy L. Putoczki
bioRxiv 2022.02.25.481888; doi: https://doi.org/10.1101/2022.02.25.481888

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