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Pizza club - January 2017 - Kamil


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Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance, Fischer et al., Nature, 2015

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Pizza club - January 2017 - Kamil

  1. 1. S Epithelial-mesenchymal transition Kamil Grzyb PhD student at ICS LCSB
  2. 2. What is EMT (or MET)
  3. 3. Where EMT is present S  EMTs are associated with S  embryo implantation, S  embryogenesis, S  organ development, S  wound healing S  But also contributes pathologically to fibrosis or cancer metastasis
  4. 4. Cancer metastasis with EMT Nature 493, 487–488 (24 January 2013)
  5. 5. Triple-transgenic mouse model ü  Mouse models of breast cancer metastasis (MMTV - PyMT) ü  Fsp1 is the critical gatekeeping gene of EMT initiation ü  Cre-switchable fluorescent marker under the control of the -actin promoter (Rosa26) – irreversible!
  6. 6. Confirming the E(RFP+) and M(GFP+) phenotype
  7. 7. Primary tumor & lung metastasis stained
  8. 8. Tumor graft for EMT 2% GFP+ 98% RFP+ GFP+ EMT tumour cells did not contribute to lung metastasis
  9. 9. Validating EMT lineage tracing system
  10. 10. EMT lineage tracing system Almost no Mesenchymal originated metastasis
  11. 11. In vivo spreading of tri-PyMT cells.
  12. 12. Inhibit EMT with miR-200
  13. 13. M cells chemoresistance(CTX) •  Mice treated with cyclophosphamide (CTX) •  60% tumor reduction (by êgrowth and éapoptosis) •  GFP+(mesenchymal) cell count remained static.
  14. 14. miR-200 cancel M resistance
  15. 15. RNA-sequencing
  16. 16. Summing up… S  Tumour cells disseminate and form metastases while persisting in their epithelial phenotype. S  miR-200 (EMT inhibitor) has no effect on metastasis S  Non-EMT cells are sensitive to chemotherapy
  17. 17. Other ways that EMT possibly contribute to cancer metastasis?
  18. 18. Tamoxifen-Cre