c-src recruitment is involved in c-MET-mediated malignant behaviour of NT2D1 non-seminoma cells

Erica Leonetti, Luisa Gesualdi, Katia Corano Scheri, Simona Dinicola, Luigi Fattore, Maria Grazia Masiello, Alessandra Cucina, Rita Mancini, Mariano Bizzarri, Giulia Ricci, Angela Catizone

Research output: Contribution to journalArticle

Abstract

c-MET pathway over-activation is the signature of malignancy acquisition or chemotherapy resistance of many cancers. We recently demonstrated that type II Testicular Germ Cell Tumours (TGCTs) express c-MET receptor. In particular, we elucidated that the non-seminoma lesions express c-MET protein at higher level, compared with the seminoma ones. In line with this observation, NTERA-2 clone D1 (NT2D1) non-seminoma cells increase their proliferation, migration and invasion in response to Hepatocyte Growth Factor (HGF). One of the well-known adaptor-proteins belonging to c-MET signaling cascade is c-Src. Activation of c-Src is related to the increase of aggressiveness of many cancers. For this reason, we focused on the role of c-Src in c-MET-triggered and HGF-dependent NT2D1 cell activities. In the present paper, we have elucidated that this adaptor-protein is involved in HGF-dependent NT2D1 cell proliferation, migration and invasion, since Src inhibitor-1 administration abrogates these responses. Despite these biological evidences western blot analyses have not revealed the increase of c-Src activation because of HGF administration. However, notably, immunofluorescence analyses revealed that cytoplasmic and membrane-associated localization of c-Src shifted to the nuclear compartment after HGF stimulation. These results shed new light in the modality of HGF-dependent c-Src recruitment, and put the basis for novel investigations on the relationship between c-Src, and TGCT aggressiveness.

Original languageEnglish
Article number320
JournalInternational Journal of Molecular Sciences
Volume20
Issue number2
DOIs
Publication statusPublished - Jan 2 2019

Keywords

  • C-MET
  • C-MET inhibitors
  • C-Src
  • Cancer therapy
  • HGF
  • Src inhibitors
  • TGCTs

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Leonetti, E., Gesualdi, L., Scheri, K. C., Dinicola, S., Fattore, L., Masiello, M. G., Cucina, A., Mancini, R., Bizzarri, M., Ricci, G., & Catizone, A. (2019). c-src recruitment is involved in c-MET-mediated malignant behaviour of NT2D1 non-seminoma cells. International Journal of Molecular Sciences, 20(2), [320]. https://doi.org/10.3390/ijms20020320