Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation
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Francesco Paolo Fiorentino1, Elvan Tokgün1, Sònia Solé-Sánchez1, Sabrina Giampaolo1, Onur Tokgün1, Toni Jauset2, Takashi Kohno3, Manuel Perucho1,4, Laura Soucek2,4,5, Jun Yokota1,3
1Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain
2Vall d’Hebron Institute of Oncology (VHIO) Hospital Vall d’Hebron, Barcelona, Spain
3Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan
4Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
5Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain
Jun Yokota, e-mail: [email protected]
Keywords: small cell lung cancer, MYC, CDKN1A, MYCL, SCLC
Received: February 18, 2016 Accepted: March 31, 2016 Published: April 18, 2016
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with high mortality. One of the MYC family genes, MYC, MYCL or MYCN, is amplified in ~20% of the SCLCs; therefore, MYC proteins are potential therapeutic targets in SCLC patients. We investigated the therapeutic impact of Omomyc, a MYC dominant negative, in a panel of SCLC cell lines. Strikingly, Omomyc suppressed the growth of all tested cell lines by inducing cell cycle arrest and/or apoptosis. Induction of G1 arrest by Omomyc was found to be dependent on the activation of CDKN1A, in part, through the TP73 pathway. Our results strongly indicate that SCLC cells carrying amplification of MYC, MYCL or MYCN are addicted to MYC function, suggesting that MYC targeting would be an efficient therapeutic option for SCLC patients.
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