Oncotarget

Research Papers:

Autophagy processes are dependent on EGF receptor signaling

Vincenzo De Iuliis, Antonio Marino, Marika Caruso, Sabrina Capodifoglio, Vincenzo Flati, Anna Marynuk, Valeria Marricareda, Sebastiano Ursi, Paola Lanuti, Claudio Talora, Pio Conti, Stefano Martinotti and Elena Toniato _

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Oncotarget. 2018; 9:30289-30303. https://doi.org/10.18632/oncotarget.25708

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Abstract

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

Correspondence to:

Elena Toniato, email: e.toniato@unich.it

Keywords: apoptosis; autophagy; Beclin 1; EGF receptor; MAPK pathway

Received: May 03, 2018     Accepted: June 13, 2018     Published: July 13, 2018

ABSTRACT

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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