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Cell. 2017 Jul 27;170(3):548-563.e16. doi: 10.1016/j.cell.2017.07.008.

Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy.

Author information

1
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute,Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
2
Department of Surgery, the University of Michigan Comprehensive Cancer Center, Graduate programs in Immunology and Cancer Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA, 48109.
3
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute,Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China; Department of Surgery, the University of Michigan Comprehensive Cancer Center, Graduate programs in Immunology and Cancer Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA, 48109.
4
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute,Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: yingxuanchen71@126.com.
5
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute,Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: haoyanchen@shsmu.edu.cn.
6
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute,Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: jiehong97@shsmu.edu.cn.
7
Department of Surgery, the University of Michigan Comprehensive Cancer Center, Graduate programs in Immunology and Cancer Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA, 48109. Electronic address: wzou@med.umich.edu.
8
State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute,Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China. Electronic address: jingyuanfang@sjtu.edu.cn.

Abstract

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.

KEYWORDS:

Colorectal cancer; F.nucleatum; Toll-like receptor; autophagy; chemoresistance; miRNA; recurrence

PMID:
28753429
PMCID:
PMC5767127
DOI:
10.1016/j.cell.2017.07.008
[Indexed for MEDLINE]
Free PMC Article

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