Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation.
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.
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.
Francesco Paolo
FP
Fiorentino
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.
Elvan
E
Tokgün
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.
Sònia
S
Solé-Sánchez
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.
Sabrina
S
Giampaolo
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.
Onur
O
Tokgün
Vall d'Hebron Institute of Oncology (VHIO) Hospital Vall d'Hebron, Barcelona, Spain.
Toni
T
Jauset
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
Takashi
T
Kohno
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.|Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
Manuel
M
Perucho
Vall d'Hebron Institute of Oncology (VHIO) Hospital Vall d'Hebron, Barcelona, Spain.|Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.|Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Laura
L
Soucek
Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Campus Can Ruti, Barcelona, Spain.|Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
Jun
J
Yokota
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D005784:Gene Amplification; D020868:Gene Silencing; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D056286:Retinoblastoma Binding Proteins / Q000235:genetics* / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human; C489427:MYC protein, human; D010446:Peptide Fragments; D016271:Proto-Oncogene Proteins c-myc; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C568271:omomyc protein; D044767:Ubiquitin-Protein Ligases
CDKN1A; MYC; MYCL; SCLC; small cell lung cancer