小柯机器人

中国医学科学院北京协和医学院Xuetao Cao和海军医科大学Qian Zhang共同合作近期取得重要工作进展，他们研究发现TAMs中葡萄糖代谢增加，通过助长溶酶体组织蛋白酶B的O-GlcNA酰化来促进癌症转移和化疗耐药。相关论文2022年9月8日在线发表于《癌细胞》杂志上。

研究人员表明M2样TAM具有较强的吸收肿瘤内葡萄糖的能力。它们增加的葡萄糖摄取促进了己糖胺生物合成途径依赖的O-GlcNAcylation促进癌症转移和化学抗性。葡萄糖代谢促进溶酶体包裹的蛋白酶B在丝氨酸210处的O-GlcNA酰化，由溶酶体定位的O-GlcNAc转移酶（OGT）介导，从而提高巨噬细胞中成熟的组织蛋白酶B及其在肿瘤微环境（TME）中的分泌。

巨噬细胞中OGT的缺失降低了TME中的O-GlcNA酰化和成熟的组织蛋白酶B，并破坏了癌症转移和化疗耐药性。人类TAM的高OGT与组织蛋白酶B的表达呈正相关，并且这两个水平都可以预测癌症患者的化疗反应和预后。他们的研究报告了促肿瘤TAM中葡萄糖代谢的生物学和潜在临床意义，并揭示了潜在的机制。

据介绍，葡萄糖代谢如何重塑肿瘤相关巨噬细胞（TAMs）的促肿瘤功能需要进一步研究。

附：英文原文

Title: Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal Cathepsin B to promote cancer metastasis and chemoresistance

Author: Qingzhu Shi, Qicong Shen, Yanfang Liu, Yang Shi, Wenwen Huang, Xi Wang, Zhiqing Li, Yangyang Chai, Hao Wang, Xiangjia Hu, Nan Li, Qian Zhang, Xuetao Cao

Issue&Volume: 2022-09-08

Abstract: How glucose metabolism remodels pro-tumor functions of tumor-associated macrophages(TAMs) needs further investigation. Here we show that M2-like TAMs bear the highestindividual capacity to take up intratumoral glucose. Their increased glucose uptakefuels hexosamine biosynthetic pathway-dependent O-GlcNAcylation to promote cancermetastasis and chemoresistance. Glucose metabolism promotes O-GlcNAcylation of thelysosome-encapsulated protease Cathepsin B at serine 210, mediated by lysosome-localizedO-GlcNAc transferase (OGT), elevating mature Cathepsin B in macrophages and its secretionin the tumor microenvironment (TME). Loss of OGT in macrophages reduces O-GlcNAcylationand mature Cathepsin B in the TME and disrupts cancer metastasis and chemoresistance.Human TAMs with high OGT are positively correlated with Cathepsin B expression, andboth levels predict chemotherapy response and prognosis of individuals with cancer.Our study reports the biological and potential clinical significance of glucose metabolismin tumor-promoting TAMs and reveals insights into the underlying mechanisms.

DOI: 10.1016/j.ccell.2022.08.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00376-2

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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