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Silencing the MET oncogene leads to regression of experimental tumors and metastases

Oncogene volume 27, pages 684–693 (2008)Cite this article

Abstract

In spite of the established knowledge of the genetic alterations responsible for cancer onset, the genes promoting and maintaining the invasive/metastatic phenotype are still elusive. The MET proto-oncogene, encoding the tyrosine kinase receptor for hepatocyte growth factor (HGF), senses unfavorable micro-environmental conditions and drives cell invasion and metastasis. MET overexpression, often induced by tumor hypoxia, leads to constitutive activation of the receptor and correlates with poor prognosis. To establish the role of MET in different phases of tumor progression, we developed an inducible lentiviral delivery system of RNA interference. Silencing the endogenous MET gene, overexpressed in tumor cells, resulted in (i) impairment of the execution of the full invasive growth program in vitro, (ii) lack of tumor growth and (iii) decreased generation of experimental metastases in vivo. Notably, silencing MET in already established metastases led to their almost complete regression. This indicates that persistent expression of the MET oncogene is mandatory until the advanced phases of cancer progression.

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Acknowledgements

We thank E Vigna and L Naldini for providing lentiviral vectors; L Tamagnone and our colleagues for helpful discussions; R Albano, R LoNoce and L Palmas for technical assistance. This study was supported by AIRC (grants to SG and PMC), MIUR (grant to SG) and Regione Piemonte (grant to SG). CM is the recipient of a Lagrange fellowship.

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Authors and Affiliations

  1. Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Torino, Italy

    S Corso, C Migliore, E Ghiso, P M Comoglio & S Giordano

  2. Unit of Pathology, Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Torino, Italy

    G De Rosa

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  1. S Corso
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  2. C Migliore
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Correspondence to S Giordano.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Corso, S., Migliore, C., Ghiso, E. et al. Silencing the MET oncogene leads to regression of experimental tumors and metastases. Oncogene 27, 684–693 (2008). https://doi.org/10.1038/sj.onc.1210697

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