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Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy.

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.
PMID
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Authors

Mayor MeshTerms
Keywords

Colorectal cancer

F.nucleatum

Toll-like receptor

autophagy

chemoresistance

miRNA

recurrence

Journal Title cell
Publication Year Start




PMID- 28753429
OWN - NLM
STAT- In-Process
DA  - 20170728
LR  - 20170728
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Linking)
VI  - 170
IP  - 3
DP  - 2017 Jul 27
TI  - Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by
      Modulating Autophagy.
PG  - 548-563.e16
LID - S0092-8674(17)30815-2 [pii]
LID - 10.1016/j.cell.2017.07.008 [doi]
AB  - 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.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Yu, TaChung
AU  - Yu T
AD  - 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.
FAU - Guo, Fangfang
AU  - Guo F
AD  - 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.
FAU - Yu, Yanan
AU  - Yu Y
AD  - 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.
FAU - Sun, Tiantian
AU  - Sun T
AD  - 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.
FAU - Ma, Dan
AU  - Ma D
AD  - 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.
FAU - Han, Jixuan
AU  - Han J
AD  - 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.
FAU - Qian, Yun
AU  - Qian Y
AD  - 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.
FAU - Kryczek, Ilona
AU  - Kryczek I
AD  - 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.
FAU - Sun, Danfeng
AU  - Sun D
AD  - 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.
FAU - Nagarsheth, Nisha
AU  - Nagarsheth N
AD  - 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.
FAU - Chen, Yingxuan
AU  - Chen Y
AD  - 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:
      [email protected]
FAU - Chen, Haoyan
AU  - Chen H
AD  - 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:
      [email protected]
FAU - Hong, Jie
AU  - Hong J
AD  - 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:
      [email protected]
FAU - Zou, Weiping
AU  - Zou W
AD  - 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: [email protected]
FAU - Fang, Jing-Yuan
AU  - Fang JY
AD  - 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:
      [email protected]
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
OTO - NOTNLM
OT  - Colorectal cancer
OT  - F.nucleatum
OT  - Toll-like receptor
OT  - autophagy
OT  - chemoresistance
OT  - miRNA
OT  - recurrence
EDAT- 2017/07/29 06:00
MHDA- 2017/07/29 06:00
CRDT- 2017/07/29 06:00
PHST- 2017/01/22 [received]
PHST- 2017/05/11 [revised]
PHST- 2017/07/10 [accepted]
AID - S0092-8674(17)30815-2 [pii]
AID - 10.1016/j.cell.2017.07.008 [doi]
PST - ppublish
SO  - Cell. 2017 Jul 27;170(3):548-563.e16. doi: 10.1016/j.cell.2017.07.008.