The Department of Biomedicine

CCBIO seminar: Angela Nieto

Epithelial plasticity in development and disease

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Angela Nieto
Developmental Neurobiology Unit, Instituto de Neurociencias CSIC-UMH, San Juan de Alicante, Spain

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 EMT promotes the delamination of cancer cells from the primary tumour in their way to form metastasis.

We have found that in cancer, similar to the situation in embryos, a reversion of EMT to 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 tumour will impede metastasis, which is the principle that has inspired efforts by academia and pharmaceutical companies to block 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 tumours from already disseminated cells. Inhibiting stem cell properties associated with the ability of initiating new tumours seems to be a safer strategy, particularly for tumours where EMT is an early event, implying that cancer cells have very likely disseminated even before the tumour 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 ameliorate fibrosis.

Selected publications:

Nieto, M.A. (2011). The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu. Rev. Cell Dev. Biol. 27, 347–76

Nieto, M.A. (2013). Epithelial plasticity: a common theme in embryonic and cancer cells. Science 342, 1234850

Chairperson: James Lorens, CCBIO