E2F1 inhibition mediates cell death of metastatic melanoma

• Published in: Cell death & disease Vol. 9; no. 5; pp. 527 - 12
• Main Authors: Rouaud, Florian, Hamouda-Tekaya, Nedra, Cerezo, Michaël, Abbe, Patricia, Zangari, Joséphine, Hofman, Veronique, Ohanna, Mickaël, Mograbi, Baharia, El-Hachem, Najla, Benfodda, Zohra, Lebeau, Alexandre, Tulic, Meri K., Hofman, Paul, Bertolotto, Corine, Passeron, Thierry, Annicotte, Jean-Sébastien, Ballotti, Robert, Rocchi, Stéphane
• Format: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing Group UK 09.05.2018; Springer Nature B.V; Nature Publishing Group
• Subjects: 13; 14/19; 38/109; 64/60; 82/29; 82/51; 96/106; 96/2; 96/31; 96/95; Antibodies; Apoptosis; Biochemistry; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biomedical and Life Sciences; Cancer; Cell Biology; Cell Culture; Cell cycle; Cell death; CTLA-4 protein; Immunology; Immunotherapy; Life Sciences; Melanoma; Metastases; Metastasis; PD-1 protein; Sciences du vivant; Senescence; Signal transduction
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0566-1

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.