Autophagy processes are dependent on EGF receptor signaling
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Vincenzo De Iuliis1, Antonio Marino1, Marika Caruso1, Sabrina Capodifoglio1, Vincenzo Flati2, Anna Marynuk3, Valeria Marricareda3, Sebastiano Ursi1, Paola Lanuti4, Claudio Talora5, Pio Conti6, Stefano Martinotti1,7 and Elena Toniato7
1Unit of Predictive Medicine, SS Annunziata University Hospital of Chieti, Chieti, Italy
2Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
3Odessa National Medical University, Odesa, Odessa Oblsat, Ucraina
4Department of Medicine and Aging Sciences, University G. d’Annunzio of Chieti, Chieti, Italy
5Department of Molecular Medicine, University of Rome “La Sapienza”, Rome, Italy
6Postgraduate Medical School, University of Chieti, Chieti, Italy
7Department of Medical, Oral and Biotechnological Sciences, University G. d’Annunzio of Chieti, Chieti, Italy
Elena Toniato, email: email@example.com
Keywords: apoptosis; autophagy; Beclin 1; EGF receptor; MAPK pathway
Received: May 03, 2018 Accepted: June 13, 2018 Published: July 13, 2018
Autophagy is a not well-understood conserved mechanism activated during nutritional deprivation in order to maintain cellular homeostasis. In the present study, we investigated the correlations between autophagy, apoptosis and the MAPK pathways in melanoma cell lines. We demonstrated that during starvation the EGF receptor mediated signaling activates many proteins involved in the MAPK pathway. Our data also suggest a previously unidentified link between the EGFR and Beclin-1 in melanoma cell line. We demonstrated that, following starvation, EGFR binds and tyrosine-phosphorylates Beclin-1, suggesting that it may play a key inhibitory role in the early stage of starvation, possibly through the Beclin-1 sequestration. Furthermore, EGFR releases Beclin-1 and allows initiating steps of the autophagic process. Interestingly enough, when the EGFR pathway was blocked by anti-EGF antibodies, immunoprecipitated Beclin-1 did not bind the phospho-EGFR. In addition, an extended binding of p-Bcl2 either with Beclin-1 or with Bax was observed with a decreased activation of the stress-induced JNK kinase, thus avoiding the transduction pathways that activate autophagy and apoptosis, respectively. For this reason, we advance the hypothesis that the activation of the EGFR is a necessary event that allows the ignition and progression of the autophagic process, at least in melanoma cells.
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