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Nature子刊:癌症中的逆向进化

摘要 : 三月九日,中山大学贺雄雷(Xionglei He)教授领导研究团队在Nature Communications杂志上发表文章指出,癌症发生过程中存在从多细胞性向单细胞性的逆向进化。

 三月九日,中山大学贺雄雷(Xionglei He)教授领导研究团队在Nature Communications杂志上发表文章指出,癌症发生过程中存在从多细胞性向单细胞性的逆向进化。

贺雄雷教授从进化的角度来理解肿瘤的发展,把单个细胞发展成肿瘤的过程看作是一个短期的细胞演化事件。文章指出,多细胞生物为了维持多细胞性演化出了一些遗传学限制。从理论上看,癌症可能就是这种限制发生崩溃导致的结果。

研究人员通过一个移植瘤的完整生活史向人们展示,癌转移的推动力来自于多细胞性相关基因上功能缺失突变的正向选择。表达分析揭示了多细胞性相关基因的显著下调,以及向胚胎干细胞演化的表达谱,胚胎干细胞的无限繁殖能力类似于单细胞生命。在漫长的进化史中,多细胞性出现就伴随着癌基因诞生率的提高。而且一般在肿瘤中,功能缺失的肿瘤抑制子要多于活化的癌基因。

这些数据说明,癌症表现为一种由功能缺失驱动的逆向进化,回到单细胞“基态”。这个癌症进化模型可以解释肿瘤间和肿瘤内的遗传异质性,帮助人们理解癌症向远端转移,有望为癌症治疗带来新的启示。

原文链接:The reverse evolution from multicellularity to unicellularity during carcinogenesis

Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-function-driven reverse evolution back to the unicellular ‘ground state’. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.

来源: Nature Communications 浏览次数:99

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