上海交通大学医学院Tong Ji，Xu Wang，Shuyang Sun和Yu Zhang共同合作，近期取得重要工作进展。他们研究发现，癌细胞能够利用伤害性感觉神经在营养不良环境中及营养饥饿疗法中茁壮成长。相关论文2022年11月16日在线发表于《细胞—代谢》杂志上。

研究人员发现，癌细胞可以利用伤害性感觉神经在营养不良的环境中茁壮成长。在初步研究口腔粘膜癌的低葡萄糖环境时，研究人员发现癌细胞利用ROS触发的c-Jun激活来分泌神经生长因子（NGF），该因子调节痛觉神经，促进降钙素基因相关肽（CGRP）的产生。神经源性CGRP随后通过Rap1介导的mTOR-Raptor相互作用的破坏在癌细胞中诱导细胞保护性自噬。基于抗糖酵解和抗血管生成的营养饥饿疗法都会加剧癌细胞和伤害性神经的恶性循环，并从FDA批准的抗迁移药物阻断神经源性CGRP中获益。

这一研究揭示，痛觉神经在营养不足的环境中和营养饥饿的疗法中为癌症进展提供有利的微环境。

据介绍，尽管营养饥饿疗法可以在多发性癌症中产生强烈的抗肿瘤效果，但已经有令人信服的证据表明，癌细胞利用肿瘤微环境在营养贫乏的环境中茁壮成长。

附：英文原文

Title: Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies

Author: Yu Zhang, Chengzhong Lin, Zheqi Liu, Yiting Sun, Mingtao Chen, Yibo Guo, Wei Liu, Chenping Zhang, Wantao Chen, Jian Sun, Ronghui Xia, Yuhua Hu, Xi Yang, Jiang Li, Zhiyuan Zhang, Wei Cao, Shuyang Sun, Xu Wang, Tong Ji

Issue&Volume: 2022-11-16

Abstract: Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiplecarcinomas, it has been convincingly demonstrated that cancer cells exploit the tumormicroenvironment to thrive in nutrient-poor environments. Here, we reveal that cancercells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initiallyexamining the low-glucose environment of oral mucosa carcinomas, we discovered thatcancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor(NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP)production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancercells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysisand anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycleof cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenicCGRP with an FDA-approved antimigraine drug. Our study sheds light on the role ofthe nociceptive nerve as a microenvironmental accomplice of cancer progression innutrient-poor environments and upon nutrient-starvation therapies.

DOI: 10.1016/j.cmet.2022.10.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00490-9