CELL:肿瘤为何“饿不死”?神经元为饥饿胰腺癌提供营养支持 

2020-11-03 haibei MedSci原创

胰腺导管腺癌(PDAC)患者的一个常见症状是神经性疼痛,可能需要进行侵入性手术来缓解。事实上,大多数PDAC肿瘤显示出神经浸润,这与患者的不良结果有关。

胰腺导管腺癌(PDAC)患者的一个常见症状是神经性疼痛,可能需要进行侵入性手术来缓解。事实上,大多数PDAC肿瘤显示出神经浸润,这与患者的不良结果有关。

沿着这些思路,PDAC的基因分析显示轴突引导调节器频繁发生突变,提示神经元支持在肿瘤发生中的作用。此外,用辣椒素手术去神经或消融神经可增加PDAC小鼠的存活率,从而支持神经在PDAC中的促癌作用。

据报道,来自背根神经节(DRG)和交感神经的感觉神经元加速了PDAC肿瘤的发生,而胆碱能神经则抑制了PDAC的生长。到目前为止,机制研究集中在释放到肿瘤中的神经营养因子或神经递质上。

胰腺导管腺癌(PDAC)肿瘤具有营养不良、去势、高度神经支配的肿瘤微环境。虽然神经元可以释放刺激因子加速PDAC肿瘤的发生,但外周轴突的代谢贡献尚未被探讨。

最近,研究人员在CELL杂志发文,其发现,在Ser/Gly(甘氨酸)剥夺期间,外周神经元轴突会释放丝氨酸(Ser)来支持外源性Ser(exSer)依赖性PDAC细胞的生长。

Ser剥夺导致六个Ser密码子中的两个,TCC和TCT上的核糖体停滞,并允许PDAC细胞选择性地翻译和分泌神经生长因子(NGF),以促进肿瘤的保全。

与此相一致的是,在无Ser/Gly饮食的小鼠中,exSer依赖性PDAC肿瘤生长较慢,并显示出增强的保留。使用Trk-NGF抑制剂LOXO-101阻断代偿性神经元支配,可以进一步降低PDAC肿瘤的生长。

因此,这些数据表明,轴突-癌症代谢串联是支持PDAC在营养不良环境下生长的关键适应手段。

 

原始出处:

Robert S. Banh et al. Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer. CELL (2020). DOI:https://doi.org/10.1016/j.cell.2020.10.016

 

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    2021-05-11 维他命
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    2020-11-04 王莉平1

    ⭐️⭐️⭐️

    0

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