Mechanism of tumor-suppressive cell competition in flies.
Mechanism of tumor-suppressive cell competition in flies.
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DOI：
10.1111/cas.14575
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发表时间：
2020-10
期刊：
影响因子：
5.7
通讯作者：
Igaki T
中科院分区：
文献类型：
--
作者：
Kanda H;Igaki T
致癌突变通常触发抗肿瘤细胞应答，例如诱导细胞凋亡或细胞衰老。过去十年的研究已经确定了第三个保护者的存在，即“细胞竞争”。细胞竞争是环境依赖性细胞消除，其中具有较高适应性的细胞通过诱导细胞死亡消除具有较低适应性的相邻细胞。虽然癌基因诱导的细胞凋亡或癌基因诱导的衰老充当细胞自主的肿瘤抑制因子，但细胞竞争通过细胞间通讯保护组织免受肿瘤发生。例如，在果蝇上皮细胞中，具有细胞极性突变的致癌细胞过度增殖并自行发展成肿瘤，但当被野生型细胞包围时，会从组织中消除。果蝇的遗传学研究揭示了这种肿瘤抑制细胞竞争至少受三种机制的调节：极性缺陷细胞和野生型细胞之间的直接细胞-细胞相互作用，上皮细胞的分泌因子，以及来自远处器官的系统性因子。肿瘤抑制细胞竞争的分子操纵可以为人类癌症提供一种新的治疗策略。细胞竞争是环境依赖性细胞消除，其中具有较高适应性的细胞通过诱导细胞死亡消除具有较低适应性的相邻细胞。在果蝇上皮细胞中，具有细胞极性突变的致癌细胞过度增殖并自行发展成肿瘤，但当被野生型细胞包围时会从组织中消除。果蝇的遗传学研究揭示了这种肿瘤抑制细胞竞争至少受三种机制的调节：极性缺陷细胞和野生型细胞之间的直接细胞-细胞相互作用，上皮细胞的分泌因子，以及来自远处器官的系统性因子。
Oncogenic mutations often trigger antitumor cellular response such as induction of apoptosis or cellular senescence. Studies in the last decade have identified the presence of the third guardian against mutation‐induced tumorigenesis, namely “cell competition.” Cell competition is a context‐dependent cell elimination whereby cells with higher fitness eliminate neighboring cells with lower fitness by inducing cell death. While oncogene‐induced apoptosis or oncogene‐induced senescence acts as a cell‐autonomous tumor suppressor, cell competition protects the tissue from tumorigenesis via cell‐cell communication. For instance, in Drosophila epithelium, oncogenic cells with cell polarity mutations overproliferate and develop into tumors on their own but are eliminated from the tissue when surrounded by wild‐type cells. Genetic studies in flies have unraveled that such tumor‐suppressive cell competition is regulated by at least three mechanisms: direct cell‐cell interaction between polarity‐deficient cells and wild‐type cells, secreted factors from epithelial cells, and systemic factors from distant organs. Molecular manipulation of tumor‐suppressive cell competition could provide a novel therapeutic strategy against human cancers. Cell competition is a context‐dependent cell elimination whereby cells with higher fitness eliminate neighboring cells with lower fitness by inducing cell death. In Drosophila epithelium, oncogenic cells with cell polarity mutations overproliferate and develop into tumors on their own but are eliminated from the tissue when surrounded by wild‐type cells. Genetic studies in flies have unraveled that such tumor‐suppressive cell competition is regulated by at least three mechanisms: direct cell‐cell interaction between polarity‐deficient cells and wild‐type cells, secreted factors from epithelial cells, and systemic factors from distant organs.
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DOI：
10.1073/pnas.1113882109
发表时间：
2012-01-10
影响因子：
11.1
作者：
Chen, Chiao-Lin;Schroeder, Molly C.;Halder, Georg
通讯作者：
Halder, Georg
影响因子：
--
作者：
Doggett K;Grusche FA;Richardson HE;Brumby AM
通讯作者：
Brumby AM
影响因子：
4.6
作者：
Abdelilah-Seyfried, S;Cox, DN;Jan, YN
通讯作者：
Jan, YN
影响因子：
5.3
作者：
Dimri, GP;Itahana, K;Campisi, J
通讯作者：
Campisi, J
影响因子：
11.8
作者：
Alpar L;Bergantiños C;Johnston LA
通讯作者：
Johnston LA