神经元释放血清以支持胰腺癌的mRNA翻译
Robert S Banh1, Douglas E Biancur1, Keisuke Yamamoto1
1Department of Radiation Oncology, Perlmutter Cancer Center, New York University Medical Center, New York, NY 10016, USA.
Cell
|November 3, 2020
概括
周围的轴突为胰腺癌细胞提供血清,在营养不良的环境中促进瘤生长. 阻断神经生长因子进一步抑制胰腺管腺癌的进展.
科学领域:
- 癌症学
- 神经科学
- 代谢过程
背景情况:
- 胰腺管腺癌 (PDAC) 瘤存在于营养贫乏,无塑性和内化的微环境中.
- 虽然神经元释放促进PDAC的因素,但外围轴突的代谢作用仍然未被探索.
研究的目的:
- 研究外围轴突对PDAC生长的代谢贡献.
- 探索轴突血清释放和PDAC细胞适应营养缺乏的相互作用.
主要方法:
- 从外围轴突释放的评估血清素 (Ser).
- 在Ser/Gly剥夺下研究PDAC细胞生长.
- 分析了 Ser 编码子和神经生长因子 (NGF) 分泌的核糖体停滞.
- 使用PDAC瘤的小鼠模型进行Ser/Gly-free饮食.
- 使用LOXO-101,一个Trk-NGF抑制剂,以阻断神经元内置.
主要成果:
- 在Ser/Gly剥夺过程中,外围轴突释放血清,支持外源性Ser (exSer) 依赖的PDAC细胞.
- 血清素缺失导致特定的血清代码 (TCC,TCT) 的核糖体停滞,促进PDAC细胞的选择性NGF转化和分泌.
- 在没有Ser/ Gly饮食的小鼠中,PDAC瘤的增长速度较慢.
- 使用LOXO-101抑制NGF信号,进一步降低了PDAC瘤的生长.
结论:
- 在营养缺乏条件下,对PDAC的适应和生长至关重要.
- 轴突的血清供应和NGF介导的内化是这种交叉通话的关键组成部分.
- 针对NGF信号提供了一个潜在的治疗策略.
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