PMID- 36068649
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20231105
IS  - 2001-3078 (Electronic)
IS  - 2001-3078 (Linking)
VI  - 11
IP  - 9
DP  - 2022 Sep
TI  - Extracellular vesicles from colorectal cancer cells promote metastasis via the 
      NOD1 signalling pathway.
PG  - e12264
LID - 10.1002/jev2.12264 [doi]
LID - e12264
AB  - Pattern-recognition receptors (PRRs) have been shown to promote tumour metastasis 
      via sensing tumour cell-derived small extracellular vesicles (EVs). 
      Nucleotide-binding oligomerisation domain 1 (NOD1), a cytoplasmic PRR, plays a 
      role in colorectal cancer (CRC) by detecting bacterial products. However, the 
      precise mechanisms underlying the effects of NOD1, following identification of 
      CRC cell-derived EVs (CRC-EVs), to potentiate CRC liver metastasis (CRC-LM), 
      remain poorly understood. Here, we demonstrate that CRC-EVs activate NOD1 in 
      macrophages to initiate secretion of inflammatory cytokines and chemokines. 
      NOD1-activated macrophages also promote CRC cell migration, while in a murine 
      model of liver metastasis (LM), NOD1-deficient mice exhibit reduced metastasis 
      following CRC-EV treatment. Furthermore, cell division cycle 42 (CDC42), a small 
      Rho guanosine-5'-triphosphate (GTP)ase, is delivered by CRC-EVs into macrophages 
      where it activates NOD1. In addition, EVs from the plasma of patients with CRC-LM 
      mediate NOD1 activation in human peripheral blood mononuclear cells. Moreover, 
      high NOD1 expression in tumour tissues is associated with poor prognosis of 
      CRC-LM. Our findings suggest that CRC-EVs activate NOD1 to promote tumour 
      metastasis, thus, NOD1 may serve as a potential target in the diagnosis and 
      treatment of CRC-LM.
CI  - (c) 2022 The Authors. Journal of Extracellular Vesicles published by Wiley 
      Periodicals, LLC on behalf of the International Society for Extracellular 
      Vesicles.
FAU - Wei, Xiduan
AU  - Wei X
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
FAU - Ye, Jingjia
AU  - Ye J
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
FAU - Pei, Yameng
AU  - Pei Y
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
FAU - Wang, Chunting
AU  - Wang C
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
FAU - Yang, Hongzhen
AU  - Yang H
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
FAU - Tian, Jingyuan
AU  - Tian J
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
FAU - Si, Guangxu
AU  - Si G
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
FAU - Ma, Yao
AU  - Ma Y
AD  - Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, P. R. China.
FAU - Wang, Kun
AU  - Wang K
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), Department of Hepatobiliary and Pancreatic Surgery Unit I, 
      Peking University Cancer Hospital & Institute, Beijing.
FAU - Liu, Gang
AU  - Liu G
AUID- ORCID: 0000-0001-5549-5686
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, P. R. China.
AD  - Key laboratory of Molecular Pharmacology and Drug Evalution (Yantai University), 
      Ministry of Education; Collaborative Innovation Center of Advanced Drug Delivery 
      System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 
      P. R. China.
LA  - eng
GR  - 81803358/National Natural Science Foundation of China/
GR  - 81703329/National Natural Science Foundation of China/
GR  - 81273364/National Natural Science Foundation of China/
GR  - 82003568/National Natural Science Foundation of China/
GR  - 817731/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Extracell Vesicles
JT  - Journal of extracellular vesicles
JID - 101610479
RN  - 0 (NOD1 protein, human)
RN  - 0 (Nod1 Signaling Adaptor Protein)
SB  - IM
MH  - Animals
MH  - *Colorectal Neoplasms
MH  - *Extracellular Vesicles/metabolism
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism
MH  - *Liver Neoplasms/metabolism
MH  - Mice
MH  - Nod1 Signaling Adaptor Protein/metabolism
MH  - Signal Transduction
PMC - PMC9448875
OTO - NOTNLM
OT  - NOD1 signalling
OT  - colorectal cancer
OT  - extracellular vesicles
OT  - metastatic liver
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have influenced the work reported in this 
      paper.
EDAT- 2022/09/07 06:00
MHDA- 2022/09/09 06:00
PMCR- 2022/09/06
CRDT- 2022/09/06 23:44
PHST- 2022/07/07 00:00 [revised]
PHST- 2021/11/29 00:00 [received]
PHST- 2022/08/24 00:00 [accepted]
PHST- 2022/09/06 23:44 [entrez]
PHST- 2022/09/07 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/09/06 00:00 [pmc-release]
AID - JEV212264 [pii]
AID - 10.1002/jev2.12264 [doi]
PST - ppublish
SO  - J Extracell Vesicles. 2022 Sep;11(9):e12264. doi: 10.1002/jev2.12264.