Epithelial plasticity in development and disease
| Dates: | 22 April 2014 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff |
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| Speaker: | M. Angela Nieto |
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This seminar is part of the Tissue Systems seminar series. The epithelial to mesenchymal transition (EMT) is required in the embryo for the formation of tissues which cells originate far from their final destination. This programme endows cells with migratory and invasive properties. Interestingly, the reverse process, known as mesenchymal to epithelial transition (MET), is also essential in embryogenesis to allow the differentiation of tissues and organs once the embryonic migratory cells reach their final destination. This epithelial plasticity also operates after the pathological activation of the EMT promotes the delamination of cancer cells from the primary tumor in their way to form metastasis.
We have found that in cancer, similar to the situation in embryos, a reversion of the EMT (MET) is necessary for metastatic colonization once malignant cells extravasate and find their niche in distant organs. This reversibility has important implications in the design of therapeutic strategies. On the one hand, fully preventing delamination from the primary tumor will impede metastasis, which is the principle that has inspired efforts by academia and pharmaceutical companies to block the EMT. However, in the light of these recent data on the need for cancer cells to revert to the epithelial phenotype for metastasis formation, inhibiting EMT could favour the formation of secondary tumors from already disseminated cells. Inhibiting stem cells properties associated with the ability of initiating new tumors seems to be a safer strategy, particularly for tumours where the EMT is an early event, implying that cancer cells have very likely disseminated even before the tumor is diagnosed.
By contrast, the EMT associated to the development of fibrosis can be considered as an end stage. Renal epithelial cells are converted to mesenchyme, leading to organ degeneration and failure. These aberrant mesenchymal cells never revert to the epithelial phenotype. Therefore, in contrast to the situation in cancer, therapeutic intervention inhibiting EMT can be envisioned as a promising strategy to amelliorate fibrosis.
Speaker
M. Angela Nieto
Organisation: Instituto de Neurociencias CSIC-UMH
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Lecture Theatre
Michael Smith Building
Manchester
