High levels of cancer aneuploidy are frequently associated with poor prognosis. To examine the relationship between aneuploidy and cancer progression, we analyzed a series of congenic cell lines that harbor single extra chromosomes. We found that across 13 different trisomic cell lines, 12 trisomies suppressed invasiveness or were largely neutral, while a single trisomy increased metastatic behavior by triggering a partial epithelial-mesenchymal transition. In contrast, we discovered that chromosomal instability activates cGAS/STING signaling but strongly suppresses invasiveness. By analyzing patient copy-number data, we demonstrate that specific aneuploidies are associated with distinct outcomes, and the acquisition of certain aneuploidies is in fact linked with a favorable prognosis. Thus, aneuploidy is not a uniform driver of malignancy, and different aneuploidies can uniquely influence tumor progression. At the same time, the gain of a single chromosome is capable of inducing a profound cell state transition, thereby linking genomic plasticity, phenotypic plasticity, and metastasis.

中文翻译：

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单染色体增益可以作为结肠癌的转移抑制剂和促进剂。

高水平的癌症非整倍体通常与不良预后相关。为了研究非整倍性与癌症进展之间的关系，我们分析了一系列含有单个额外染色体的同源细胞系。我们发现，在 13 种不同的三体细胞系中，12 种三体性抑制侵袭性或基本上呈中性，而单一三体性通过触发部分上皮-间质转化而增加转移行为。相反，我们发现染色体不稳定性会激活 cGAS/STING 信号传导，但会强烈抑制侵袭性。通过分析患者拷贝数数据，我们证明特定的非整倍性与不同的结果相关，并且某些非整倍性的获得实际上与良好的预后相关。因此，非整倍性并不是恶性肿瘤的统一驱动因素，不同的非整倍性可以独特地影响肿瘤进展。同时，单个染色体的获得能够诱导深刻的细胞状态转变，从而将基因组可塑性、表型可塑性和转移联系起来。