神經元釋放絲氨酸以支持胰腺癌mRNA翻譯
作者：
小柯機器人發布時間：2020/11/5 12:54:03
美國紐約大學Alec C. Kimmelman及其團隊探明，神經元釋放絲氨酸（Ser）以支持胰腺癌mRNA的翻譯。這一研究成果於2020年11月2日發表在《細胞》雜誌上。
他們發現外圍軸突釋放Ser，以支持Ser / Gly（甘氨酸）剝奪期間，外源性Ser（exSer）依賴的胰腺導管腺癌（PDAC）細胞的生長。絲氨酸剝奪導致核糖體停滯在六個絲狀齒中的兩個上，分別是TCC和TCT，並允許PDAC細胞選擇性翻譯和分泌神經生長因子（NGF）來促進腫瘤神經支配。與此相一致，exSer依賴的PDAC腫瘤在不含Ser / Gly的飲食中的膠束中生長更慢，神經支配能力增強。
使用Trk-NGF抑制劑LOXO-101阻斷代償神經元神經支配，進一步降低了PDAC腫瘤的生長。他們的數據表明軸突-癌症代謝串擾是在營養不良環境中支持PDAC生長的關鍵適應措施。
據了解，PDAC腫瘤具有營養不足、增生和高度神經支配的腫瘤微環境。儘管神經元可以釋放刺激因子以加速PDAC的腫瘤發生，但尚未探索外周軸突的代謝作用。
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
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216