Cell：大肠癌耐化疗药，细菌是帮凶

本文是2017年6月27日，美国密西根大学邹伟平主导(Lead Contact)，上海交通大学附属仁济医院房静远、陈萦晅、洪洁和陈豪燕共同通讯，发表在Cell杂志上的重量级研究成果，这是2017年迄今为止中国团队参与和组织的最高水平肠道菌群相关研究。

标题：核粒梭菌通过调节自噬来促进对大肠癌的药物抗性

中文摘要：

亮点

• 化疗后的结肠癌复发与特异的肠道微生物相关
• 核粒梭菌通过Toll样受体、microRNAs和自噬网络控制癌症的化疗抵抗；
• 监测和靶向核粒梭菌可能对病人的预后防治有意义。

摘要

肠道菌群与慢性炎症致癌作用相关。结肠癌病人的化疗失败是复发及恢复差的主因。
本研究关注肠道菌群在化疗病人中的作用。在化疗后复发的大肠癌患者的癌组织中，发现核粒梭菌的丰度占优，并与病人的临床病理特征相关；通过生物信息学和功能分析发现核粒梭菌促进针对化疗的大肠癌耐药；相关机制是：核粒梭菌靶向TLR4、MYD88先天免疫信号和特定的微小RNA，激活自噬通路并改变大肠癌的化疗响应；未来可通过检测和靶向核粒梭菌及相关信号通路，对大肠癌的临床管理产生重要价值，并可能改善大肠癌患者的预后。

英文摘要原文

Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy

Highlights

• Specific gut microbes track with post-chemotherapy recurrence of colorectal cancer
• F. nucleatum orchestrates the Toll-like receptor, microRNAs, and autophagy network to control cancer chemoresistance
• Measuring and targeting F. nucleatum may be useful for patient prognosis and management

Summary

Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes.

Cell同期配发文章导读

Cell：细菌促进大肠癌药物抗性的机制被明确！
原标题：药物，细菌和肿瘤：核粒梭菌在大肠癌中促进药物抗性
- Yu等人在新的研究中明确，核粒梭菌在复发性大肠癌患者体内帮助癌细胞增强对化疗药物的抗性；
- 这具有重大的基础研究和临床意义，对开发靶向细菌或相关信号通路的治疗和监测方法具有重要意义；
- 后续研究可以深究是否有其他革兰氏阴性菌也参与对药物抗性的促进作用；
- 对临床应用来说，也还存在的挑战是，目前即便明确就是核粒梭菌是关键性病原菌，也还没有有效的靶向性方法可以在肠道特异性清除它。

更多文章解读和背景介绍，请阅读昨天转载的bioart文章。

Reference

1. http://www.cell.com/cell/fulltext/S0092-8674(17)30815-2
2. http://www.xunludkp.com/papers/read/1070944684?kf=xread_daily
3. https://mp.weixin.qq.com/s?__biz=MzA3MzQyNjY1MQ%3D%3D&mid=2652454477&idx=5&sn=ec7f954a0c1b06ec418b31d04f37e427&scene=45#wechat_redirect
4. http://www.cell.com/cell/fulltext/S0092-8674(17)30825-5
5. http://www.xunludkp.com/papers/read/1070944684?kf=xread_daily