Somatic selection for and against cancer
Somatic selection for and against cancer
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DOI：
10.1016/s0022-5193(03)00267-4
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发表时间：
2003-12-07
影响因子：
2
通讯作者：
Nowak, MA
中科院分区：
文献类型：
--
作者：
Michor, F;Frank, SA;Nowak, MA
在多细胞生物中，细胞在明确的发育程序中合作。癌症是这种合作的崩溃：细胞突变为不协调增殖的表型。我们研究影响癌症发生率的实体组织结构的基本原理。特别是，我们探索体细胞选择如何预防或促进癌症。具有癌基因或抑癌基因突变的细胞通常具有增加的增殖率。体细胞选择增加了它们的丰度，从而增加了患癌症的风险。然而，许多潜在有害的突变会增加触发细胞凋亡的可能性，因此最初会导致细胞净增殖率降低。这些细胞通过体细胞选择被消除，因此也可以降低患癌症的风险。我们证明，将组织组织成小隔室可以避免癌基因和抑癌基因突变的快速扩散，但会促进遗传不稳定性。在小隔室中，遗传不稳定性（赋予细胞选择性劣势）可以通过随机漂移传播。如果有害突变和有利突变都参与肿瘤的发生，那么我们就会找到隔室大小的中间最佳值。 (C) 2003 Elsevier Ltd. 保留所有权利。
In multicellular organisms, cells cooperate within a well-defined developmental program. Cancer is a breakdown of such cooperation: cells mutate to phenotypes of uncoordinated proliferation. We study basic principles of the architecture of solid tissues that influence the rate of cancer initiation. In particular, we explore how somatic selection acts to prevent or to promote cancer. Cells with mutations in oncogenes or tumor suppressor genes often have increased proliferation rates. Somatic selection increases their abundance and thus enhances the risk of cancer. Many potentially harmful mutations, however, increase the probability of triggering apoptosis and, hence, initially lead to cells with reduced net proliferation rates. Such cells are eliminated by somatic selection, which therefore also works to reduce the risk of cancer. We show that a tissue organization into small compartments avoids the rapid spread of mutations in oncogenes and tumor suppressor genes, but promotes genetic instability. In small compartments, genetic instability, which confers a selective disadvantage for the cell, can spread by random drift. If both deleterious and advantageous mutations participate in tumor initiation, then we find an intermediate optimum for the compartment size. (C) 2003 Elsevier Ltd. All rights reserved.