May 30, 2020

MAX Functions as a Tumor Suppressor and Rewires Metabolism in Small Cell Lung Cancer

Cancer Cell
Arnaud AugertDavid MacPherson

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.

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Mentioned in this Paper

Neoplasms
Small Cell Carcinoma of Lung
Test Result
Genes
Metabolism
MAX
Lethal
Serine
Transformation, Genetic
Tumor Suppressor Genes

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