Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown. We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells. We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.

中文翻译：

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神经干有助于细胞致瘤性

先前的研究表明癌症对神经的依赖性。最近，越来越多的研究表明，癌细胞与神经干/祖细胞具有相同的特性和调控网络。但是，神经干性和细胞致瘤性之间的关系尚不清楚。我们表明神经干/祖细胞，但非神经胚或体干/祖细胞类型不显示出致瘤性，并且当它们通过移植到免疫缺陷中而置于非自然环境中时，所有胚层的分化成组织类型的潜力裸鼠。同样，能够引发肿瘤的癌细胞也具有神经干特性，因为它们具有在神经干细胞特有的无血清培养基中形成神经球的能力以及分化潜能，除了以前表征的神经元分化潜能。此外，没有致瘤性的成肌细胞中前分化因子的丧失导致成肌细胞身份的丧失，并获得了神经干性，致瘤性和再分化潜能。相比之下，通过分化丧失神经干导致致瘤性的丧失。这些提示神经干性的特性有助于细胞的致瘤性，而肿瘤表型异质性可能是神经干性分化潜能的影响。生物信息学分析表明，神经基因除了在神经发育中的作用外，还与胚胎发育和癌症相关。而非神经基因则不是。大多数神经特异性基因出现在典型物种中，代表进化过程中从单细胞向多细胞的过渡。短尾单胞菌（Monosiga brevicollis）中的基因是后生动物中最接近的近亲，是偏向神经细胞的基因。我们建议神经干性的性质是细胞致瘤性的来源。这是因为神经偏向的单细胞状态是多细胞性的基础状态，因此在进化过程中细胞类型多样化或分化，而肿瘤发生是沿着默认路径预先确定的默认途径恢复体细胞神经基础状态的过程。神经状态的进化优势。最接近的后生动物的单细胞物种偏向神经细胞。我们建议神经干性的性质是细胞致瘤性的来源。这是因为神经偏向的单细胞状态是多细胞性的基础状态，因此在进化过程中细胞类型多样化或分化，而肿瘤发生是沿着默认路径预先确定的默认途径恢复体细胞神经基础状态的过程。神经状态的进化优势。最接近的后生动物的单细胞物种偏向神经细胞。我们建议神经干性的性质是细胞致瘤性的来源。这是因为神经偏向的单细胞状态是多细胞性的基础状态，因此在进化过程中细胞类型多样化或分化，而肿瘤发生是沿着默认路径预先确定的默认途径恢复体细胞神经基础状态的过程。神经状态的进化优势。