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Open AccessArticle

c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells

1
Department of Anatomy, Histology, Forensic-Medicine and Orthopedics, “Sapienza” University of Rome, 00161 Rome, Italy
2
Department of Surgery “Pietro Valdoni”, “Sapienza” University of Rome, 00161 Rome, Italy
3
Department of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, Italy
4
IRCCS, Regina Elena National Cancer Institute, 00144 Rome, Italy
5
Azienda Policlinico Umberto I, 00161 Rome, Italy
6
Department of Molecular and Clinical Medicine, “Sapienza” University of Rome, 00189 Rome, Italy
7
Systems Biology Group Lab, 00161 Rome, Italy
8
Department of Experimental Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(2), 320; https://doi.org/10.3390/ijms20020320
Received: 14 December 2018 / Revised: 9 January 2019 / Accepted: 10 January 2019 / Published: 14 January 2019
(This article belongs to the Special Issue Hepatocyte Growth Factor (HGF))
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. View Full-Text
Keywords: TGCTs; c-MET; HGF; c-MET inhibitors; c-Src; Src inhibitors; cancer therapy TGCTs; c-MET; HGF; c-MET inhibitors; c-Src; Src inhibitors; cancer therapy
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Leonetti, E.; Gesualdi, L.; Corano Scheri, K.; Dinicola, S.; Fattore, L.; Masiello, M.G.; Cucina, A.; Mancini, R.; Bizzarri, M.; Ricci, G.; Catizone, A. c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells. Int. J. Mol. Sci. 2019, 20, 320.

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