Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation

Francesco Paolo Fiorentino, Elvan Tokgün, Sònia Solé-Sánchez, Sabrina Giampaolo, Onur Tokgün, Toni Jauset, Takashi Kohno, Manuel Perucho, Laura Soucek, Jun Yokota

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)31014-31028
JournalOncotarget
Volume7
Issue number21
DOIs
Publication statusPublished - 24 May 2016

Keywords

  • CDKN1A
  • MYC
  • MYCL
  • SCLC
  • Small cell lung cancer

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