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

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...

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Autores principales: Leonetti, Erica, Gesualdi, Luisa, Corano Scheri, Katia, Dinicola, Simona, Fattore, Luigi, Masiello, Maria Grazia, Cucina, Alessandra, Mancini, Rita, Bizzarri, Mariano, Ricci, Giulia, Catizone, Angela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358843/
https://www.ncbi.nlm.nih.gov/pubmed/30646583
http://dx.doi.org/10.3390/ijms20020320
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author Leonetti, Erica
Gesualdi, Luisa
Corano Scheri, Katia
Dinicola, Simona
Fattore, Luigi
Masiello, Maria Grazia
Cucina, Alessandra
Mancini, Rita
Bizzarri, Mariano
Ricci, Giulia
Catizone, Angela
author_facet Leonetti, Erica
Gesualdi, Luisa
Corano Scheri, Katia
Dinicola, Simona
Fattore, Luigi
Masiello, Maria Grazia
Cucina, Alessandra
Mancini, Rita
Bizzarri, Mariano
Ricci, Giulia
Catizone, Angela
author_sort Leonetti, Erica
collection PubMed
description 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.
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spelling pubmed-63588432019-02-06 c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells Leonetti, Erica Gesualdi, Luisa Corano Scheri, Katia Dinicola, Simona Fattore, Luigi Masiello, Maria Grazia Cucina, Alessandra Mancini, Rita Bizzarri, Mariano Ricci, Giulia Catizone, Angela Int J Mol Sci Article 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. MDPI 2019-01-14 /pmc/articles/PMC6358843/ /pubmed/30646583 http://dx.doi.org/10.3390/ijms20020320 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Leonetti, Erica
Gesualdi, Luisa
Corano Scheri, Katia
Dinicola, Simona
Fattore, Luigi
Masiello, Maria Grazia
Cucina, Alessandra
Mancini, Rita
Bizzarri, Mariano
Ricci, Giulia
Catizone, Angela
c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells
title c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells
title_full c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells
title_fullStr c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells
title_full_unstemmed c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells
title_short c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells
title_sort c-src recruitment is involved in c-met-mediated malignant behaviour of nt2d1 non-seminoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358843/
https://www.ncbi.nlm.nih.gov/pubmed/30646583
http://dx.doi.org/10.3390/ijms20020320
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