Whole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of tumour expansion that are induced by the tumour suppressor TRP53. We discovered that the absence of Arrestin domain containing 3 (ARRDC3) increases the survival and long-term competitiveness of MYC-driven lymphoma cells when treated with anti-cancer agents that activate TRP53. Deleting Arrdc3 in mice caused perinatal lethality due to various developmental abnormalities, including cardiac defects. Notably, the absence of ARRDC3 markedly accelerated MYC-driven lymphoma development. Thus, ARRDC3 is a new mediator of TRP53-mediated suppression of tumour expansion, and this discovery may open new avenues to harness this process for cancer therapy.

使用 CRISPR 技术的全基因组筛选是识别新型肿瘤抑制因子以及影响恶性细胞对抗癌药物反应的因素的强大工具。将这种方法应用于淋巴瘤细胞，我们进行了全基因组筛选，以确定由肿瘤抑制因子 TRP53 诱导的新型肿瘤扩张抑制剂。我们发现，当用激活 TRP53 的抗癌药物治疗时，含有 Arrestin 结构域 3 (ARRDC3) 的缺失会增加 MYC 驱动的淋巴瘤细胞的存活率和长期竞争力。删除小鼠中的 Arrdc3 会导致围产期因各种发育异常（包括心脏缺陷）而死亡。值得注意的是，ARRDC3 的缺失显着加速了 MYC 驱动的淋巴瘤的发展。因此，ARRDC3是TRP53介导的肿瘤扩张抑制的新介质，这一发现可能为利用这一过程进行癌症治疗开辟新途径。