| Literature DB >> 32470392 |
Arnaud Augert1, Haritha Mathsyaraja2, Ali H Ibrahim1, Brian Freie2, Michael J Geuenich3, Pei-Feng Cheng2, Sydney P Alibeckoff4, Nan Wu1, Joseph B Hiatt1, Ryan Basom5, Adi Gazdar6, Lucas B Sullivan4, Robert N Eisenman7, David MacPherson8.
Abstract
Small cell lung cancer (SCLC) is a highly aggressive and lethal neoplasm. To identify candidate tumor suppressors we applied CRISPR/Cas9 gene inactivation screens to a cellular model of early-stage SCLC. Among the top hits was MAX, the obligate heterodimerization partner for MYC family proteins that is mutated in human SCLC. Max deletion increases growth and transformation in cells and dramatically accelerates SCLC progression in an Rb1/Trp53-deleted mouse model. In contrast, deletion of Max abrogates tumorigenesis in MYCL-overexpressing SCLC. Max deletion in SCLC resulted in derepression of metabolic genes involved in serine and one-carbon metabolism. By increasing serine biosynthesis, Max-deleted cells exhibit resistance to serine depletion. Thus, Max loss results in metabolic rewiring and context-specific tumor suppression.Entities:
Keywords: CRISPR-Cas9 genetic screens; MAX; MYC; SCLC; Transcriptional regulation; cancer; mouse model; serine and one-carbon metabolism; small cell lung cancer; tumor suppressor genes
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Year: 2020 PMID： 32470392 PMCID： PMC7363581 DOI： 10.1016/j.ccell.2020.04.016
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743