小柯机器人

美国纽约大学Alec C. Kimmelman及其团队探明，神经元释放丝氨酸（Ser）以支持胰腺癌mRNA的翻译。这一研究成果于2020年11月2日发表在《细胞》杂志上。

他们发现外围轴突释放Ser，以支持Ser / Gly（甘氨酸）剥夺期间，外源性Ser（exSer）依赖的胰腺导管腺癌（PDAC）细胞的生长。丝氨酸剥夺导致核糖体停滞在六个丝状齿中的两个上，分别是TCC和TCT，并允许PDAC细胞选择性翻译和分泌神经生长因子（NGF）来促进肿瘤神经支配。与此相一致，exSer依赖的PDAC肿瘤在不含Ser / Gly的饮食中的胶束中生长更慢，神经支配能力增强。

使用Trk-NGF抑制剂LOXO-101阻断代偿神经元神经支配，进一步降低了PDAC肿瘤的生长。他们的数据表明轴突-癌症代谢串扰是在营养不良环境中支持PDAC生长的关键适应措施。

据了解，PDAC肿瘤具有营养不足、增生和高度神经支配的肿瘤微环境。尽管神经元可以释放刺激因子以加速PDAC的肿瘤发生，但尚未探索外周轴突的代谢作用。

附：英文原文

Title: Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer

Author: Robert S. Banh, Douglas E. Biancur, Keisuke Yamamoto, Albert S.W. Sohn, Beth Walters, Miljan Kuljanin, Ajami Gikandi, Huamin Wang, Joseph D. Mancias, Robert J. Schneider, Michael E. Pacold, Alec C. Kimmelman

Issue&Volume: 2020-11-02

Abstract: Pancreatic ductal adenocarcinoma (PDAC) tumors have a nutrient-poor, desmoplastic,and highly innervated tumor microenvironment. Although neurons can release stimulatoryfactors to accelerate PDAC tumorigenesis, the metabolic contribution of peripheralaxons has not been explored. We found that peripheral axons release serine (Ser) tosupport the growth of exogenous Ser (exSer)-dependent PDAC cells during Ser/Gly (glycine)deprivation. Ser deprivation resulted in ribosomal stalling on two of the six Sercodons, TCC and TCT, and allowed the selective translation and secretion of nervegrowth factor (NGF) by PDAC cells to promote tumor innervation. Consistent with this,exSer-dependent PDAC tumors grew slower and displayed enhanced innervation in miceon a Ser/Gly-free diet. Blockade of compensatory neuronal innervation using LOXO-101,a Trk-NGF inhibitor, further decreased PDAC tumor growth. Our data indicate that axonal-cancermetabolic crosstalk is a critical adaptation to support PDAC growth in nutrient poor environments.

DOI: 10.1016/j.cell.2020.10.016

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31322-2