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.

C-Src recruitment is Involved in c-MET-mediated malignant behaviour of NT2D1 non-seminoma cells / Leonetti, Erica; Gesualdi, Luisa; Scheri, Katia Corano; Dinicola, Simona; Fattore, Luigi; Masiello, Maria Grazia; Cucina, Alessandra; Mancini, Rita; Bizzarri, Mariano; Ricci, Giulia; Catizone, Angela. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 20:2(2019), pp. 1-21. [10.3390/ijms20020320]

C-Src recruitment is Involved in c-MET-mediated malignant behaviour of NT2D1 non-seminoma cells

Leonetti, Erica;GESUALDI, LUISA;Scheri, Katia Corano;Dinicola, Simona;Fattore, Luigi;Mancini, Rita;Bizzarri, Mariano;Catizone, Angela
2019

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.
2019
c-MET; c-MET inhibitors; c-Src; cancer therapy; HGF; Src inhibitors; TGCTs; catalysis; molecular biology; spectroscopy; computer science applications; 1707 computer vision and pattern recognition; physical and theoretical chemistry; organic chemistry; inorganic chemistry
01 Pubblicazione su rivista::01a Articolo in rivista
C-Src recruitment is Involved in c-MET-mediated malignant behaviour of NT2D1 non-seminoma cells / Leonetti, Erica; Gesualdi, Luisa; Scheri, Katia Corano; Dinicola, Simona; Fattore, Luigi; Masiello, Maria Grazia; Cucina, Alessandra; Mancini, Rita; Bizzarri, Mariano; Ricci, Giulia; Catizone, Angela. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 20:2(2019), pp. 1-21. [10.3390/ijms20020320]
File allegati a questo prodotto
File Dimensione Formato  
Leonetti_C-Src Recruitment_2019.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 884.67 kB
Formato Adobe PDF
884.67 kB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1227713
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 9
social impact