美国弗雷德·哈钦森癌症研究中心David MacPherson和Robert N. Eisenman小组，合作发现MAX在小细胞肺癌（SCLC）中起抑癌作用并改变了细胞代谢。该研究于2020年5月28日在线发表于国际学术期刊《癌细胞》杂志。

为了发现潜在的肿瘤抑制因子，研究人员将CRISPR / Cas9基因失活筛选应用于早期SCLC的细胞模型。研究揭示最具潜力的抑癌基因是MAX，它是人SCLC中MYC家族蛋白突变的固有异二聚体伴侣。Max缺失增加了Rb1 / Trp53缺陷小鼠中细胞的生长和转化，并显著增加了SCLC进展。

相反，Max的缺失消除了MYCL过表达造成的SCLC肿瘤发生。SCLC中Max缺失抑制了参与丝氨酸和一碳代谢基因的表达。通过增加丝氨酸的生物合成，Max缺失的细胞表现出对丝氨酸缺乏的抗性。 因此，Max缺失导致代谢重塑以及背景特异性肿瘤的抑制。

附：英文原文

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

Author: Arnaud Augert, Haritha Mathsyaraja, Ali H. Ibrahim, Brian Freie, Michael J. Geuenich, Pei-Feng Cheng, Sydney P. Alibeckoff, Nan Wu, Joseph B. Hiatt, Ryan Basom, Adi Gazdar, Lucas B. Sullivan, Robert N. Eisenman, David MacPherson

Issue&Volume: 2020-05-28

Abstract: Small cell lung cancer (SCLC) is a highly aggressive and lethal neoplasm. To identifycandidate tumor suppressors we applied CRISPR/Cas9 gene inactivation screens to acellular model of early-stage SCLC. Among the top hits was MAX, the obligate heterodimerizationpartner for MYC family proteins that is mutated in human SCLC. Max deletion increases growth and transformation in cells and dramatically acceleratesSCLC 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 andone-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.

DOI: 10.1016/j.ccell.2020.04.016

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30215-4