Abstract

Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite advancements in targeted therapies (BRAF inhibitors) or immunotherapies (anti-CTLA-4 or anti-PD1), most patients with melanoma will need additional treatment. Thus, there is an urgent need to develop new therapeutical approaches to bypass resistance and achieve more prolonged responses. In this context, we were interested in E2F1, a transcription factor that plays a major role in the control of cell cycle under physiological and pathological conditions. Here we confirmed that E2F1 is highly expressed in melanoma cells. Inhibition of E2F1 activity further increased melanoma cell death and senescence, both in vitro and in vivo. Moreover, blocking E2F1 also induced death of melanoma cells resistant to BRAF inhibitors. In conclusion, our studies suggest that targeting the E2F1 signaling pathway may be therapeutically relevant for melanoma.

Details

Title
E2F1 inhibition mediates cell death of metastatic melanoma
Author
Rouaud, Florian 1 ; Hamouda-Tekaya, Nedra 1 ; Cerezo, Michaël 1 ; Abbe, Patricia 1 ; Zangari, Joséphine 2 ; Hofman, Veronique 3 ; Ohanna, Mickaël 1 ; Mograbi, Baharia 2 ; El-Hachem, Najla 1 ; Benfodda, Zohra 4 ; Lebeau, Alexandre 4 ; Tulic, Meri K 1 ; Hofman, Paul 3 ; Bertolotto, Corine 5 ; Passeron, Thierry 6 ; Annicotte, Jean-Sébastien 7 ; Ballotti, Robert 5 ; Rocchi, Stéphane 1 

 INSERM, U1065, team 12, Study of molecular mechanisms involved in pigmentation and melanoma using translational approaches, Centre Méditerranéen de Médecine Moléculaire (C3M), Nice, France; Université Cote d’azur, UFR de Médecine, Nice, France 
 Université Cote d’azur, UFR de Médecine, Nice, France; Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Nice, France 
 Université Cote d’azur, UFR de Médecine, Nice, France; Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Nice, France; Laboratoire de pathologie clinique et expérimentale et Hospital-related biobank (BB-0033-00025), Hôpital Pasteur, Nice, France 
 Laboratoire de Détection, évaluation gestion des risques émergents et chroniques, Université de Nimes, Nîmes, France 
 Université Cote d’azur, UFR de Médecine, Nice, France; Centre Méditerranéen de Médecine Moléculaire (C3M), Team 1, INSERM U1065, Nice, France 
 INSERM, U1065, team 12, Study of molecular mechanisms involved in pigmentation and melanoma using translational approaches, Centre Méditerranéen de Médecine Moléculaire (C3M), Nice, France; Service de Dermatologie, Hôpital Archet II, CHU de Nice, Nice, France 
 CNRS, Institut Pasteur de Lille, UMR 8199–EGID, Université de Lille, Lille, France 
Pages
1-12
Publication year
2018
Publication date
May 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2054144397
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.