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


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.

SUBMITTER: Fiorentino FP 

PROVIDER: S-EPMC5058735 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Fiorentino Francesco Paolo FP   Tokgün Elvan E   Solé-Sánchez Sònia S   Giampaolo Sabrina S   Tokgün Onur O   Jauset Toni T   Kohno Takashi T   Perucho Manuel M   Soucek Laura L   Yokota Jun J  

Oncotarget 20160501 21


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 O  ...[more]

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