Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective.

Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective.
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癌症吸引子:从基因网络动力学和发育视角的肿瘤的系统视图。

DOI:
10.1016/j.semcdb.2009.07.003
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发表时间:
2009-09
影响因子:
7.3
通讯作者:
Kauffman S
Kauffman S
中科院分区:
生物学2区
文献类型:
--
作者:
Huang S;Ernberg I;Kauffman S

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细胞谱系定型和分化受复杂的基因调控网络控制。不适当的调节信号和网络的突变性重新布线破坏这些过程可导致肿瘤发生。癌细胞通常表现出不成熟或胚胎特征,并且失调的发育基因可以作为致癌基因。然而,体细胞进化和多步骤肿瘤发生的流行范式,虽然在许多情况下是有用的,但没有提供逻辑上连贯的原因,为什么肿瘤发生重演个体发生。从基因调控网络的综合、复杂系统方法中衍生出的“癌症吸引子”的正式概念可能提供了一个自然的解释。在这里,我们提出了基因网络动力学中的吸引子理论,并回顾了吸引子的细胞类型的概念。我们认为,癌细胞被困在异常吸引子,并讨论了这一概念,在癌症生物学,包括癌症基因组学和癌症干细胞,以及分化治疗的影响,在最近的想法。
Cell lineage commitment and differentiation are governed by a complex gene regulatory network. Disruption of these processes by inappropriate regulatory signals and by mutational rewiring of the network can lead to tumorigenesis. Cancer cells often exhibit immature or embryonic traits and dysregulated developmental genes can act as oncogenes. However, the prevailing paradigm of somatic evolution and multi-step tumorigenesis, while useful in many instances, offers no logically coherent reason for why oncogenesis recapitulates ontogenesis. The formal concept of “cancer attractors”, derived from an integrative, complex systems approach to gene regulatory network may provide a natural explanation. Here we present the theory of attractors in gene network dynamics and review the concept of cell types as attractors. We argue that cancer cells are trapped in abnormal attractors and discuss this concept in the light of recent ideas in cancer biology, including cancer genomics and cancer stem cells, as well as the implications for differentiation therapy.
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