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Invasive growth: a MET-driven genetic programme for cancer and stem cells

Abstract

Metastasis follows the inappropriate activation of a genetic programme termed invasive growth, which is a physiological process that occurs during embryonic development and post-natal organ regeneration. Burgeoning evidence indicates that invasive growth is also executed by stem and progenitor cells, and is usurped by cancer stem cells. The MET proto-oncogene, which is expressed in both stem and cancer cells, is a key regulator of invasive growth. Recent findings indicate that the MET tyrosine-kinase receptor is a sensor of adverse microenvironmental conditions (such as hypoxia) and drives cell invasion and metastasis through the transcriptional activation of a set of genes that control blood coagulation.

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Figure 1: Invasive growth is a morphogenic programme in the embryo.
Figure 2: MET expression in stem cells.
Figure 3: Interplay between MET and self-renewal signalling pathways.
Figure 4: Hypoxia activates the MET promoter.
Figure 5: MET drives the journey from hypoxia to normoxia (passing through a fibrin trail).

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Acknowledgements

We thank Livio Trusolino for the critical reading of the manuscript and Antonella Cignetto for excellent assistance. The work from the authors' laboratory is supported by research grants awarded by AIRC (Associazione Italiana per la Ricerca sul Cancro), and by the Foundations CRT and Compagnia di San Paolo.

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Correspondence to Carla Boccaccio or Paolo M. Comoglio.

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National Cancer Institute

breast carcinomas

colorectal carcinomas

gastric cancer

glioblastomas

melanomas

osteosarcomas

rhabdomyosarcomas

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Boccaccio, C., Comoglio, P. Invasive growth: a MET-driven genetic programme for cancer and stem cells. Nat Rev Cancer 6, 637–645 (2006). https://doi.org/10.1038/nrc1912

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