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从神经元中汲取的使癌细胞静止的经验教训。

Lessons we can learn from neurons to make cancer cells quiescent.

机构信息

Laboratorio de Biología Molecular y Neurociencias, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca, Mexico.

出版信息

J Neurosci Res. 2019 Sep;97(9):1141-1152. doi: 10.1002/jnr.24428. Epub 2019 Apr 15.

Abstract

Cancer is a major concern for contemporary societies. However, the incidence of cancer is unevenly distributed among tissues and cell types. In particular, the evidence indicates that neurons are absolutely resistant to cancer and this is commonly explained on the basis of the known postmitotic state of neurons. The dominant paradigm on cancer understands this problem as a disease caused by mutations in cellular genes that result in unrestrained cell proliferation and eventually in tissue invasion and metastasis. However, the evidence also shows that mutations and gross chromosomal anomalies are common in functional neurons that nevertheless do not become neoplastic. This fact suggests that in the real nonexperimental setting mutations per se are not enough for inducing carcinogenesis but also that the postmitotic state of neurons is not genetically controlled or determined, otherwise there should be reports of spontaneously transformed neurons. Here we discuss the evidence that the postmitotic state of neurons has a structural basis on the high stability of their nuclear higher order structure that performs like an absolute tumor suppressor. We also discuss evidence that it is possible to induce a similar structural postmitotic state in nonneural cell types as a practical strategy for stopping or reducing the progression of cancer.

摘要

癌症是当代社会的主要关注点。然而,癌症的发病率在组织和细胞类型之间分布不均。特别是,有证据表明神经元绝对不会患上癌症,这通常可以根据神经元的已知有丝后状态来解释。关于癌症的主导范式将这个问题理解为一种由细胞基因中的突变引起的疾病,这些突变导致不受控制的细胞增殖,最终导致组织侵袭和转移。然而,证据也表明,突变和染色体的严重异常在功能神经元中很常见,但它们并不会变成肿瘤。这一事实表明,在实际的非实验环境中,突变本身不足以引发致癌作用,而且神经元的有丝后状态不是由遗传控制或决定的,否则应该有自发转化神经元的报道。在这里,我们讨论了证据表明,神经元的有丝后状态具有结构基础,其核高级结构具有高度稳定性,起到了绝对的肿瘤抑制作用。我们还讨论了一种可能的情况,即在非神经细胞类型中诱导类似的结构有丝后状态,作为阻止或减缓癌症进展的实用策略。

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