PMID- 31956962
OWN - NLM
STAT- MEDLINE
DCOM- 20201116
LR  - 20210429
IS  - 1674-8018 (Electronic)
IS  - 1674-800X (Print)
IS  - 1674-800X (Linking)
VI  - 11
IP  - 3
DP  - 2020 Mar
TI  - Activation of the pattern recognition receptor NOD1 augments colon cancer 
      metastasis.
PG  - 187-201
LID - 10.1007/s13238-019-00687-5 [doi]
AB  - While emerging data suggest nucleotide oligomerization domain receptor 1 (NOD1), 
      a cytoplasmic pattern recognition receptor, may play an important and 
      complementary role in the immune response to bacterial infection, its role in 
      cancer metastasis is entirely unknown. Hence, we sought to determine the effects 
      of NOD1 on metastasis. NOD1 expression in paired human primary colon cancer, 
      human and murine colon cancer cells were determined using immunohistochemistry 
      and immunoblotting (WB). Clinical significance of NOD1 was assessed using TCGA 
      survival data. A series of in vitro and in vivo functional assays, including 
      adhesion, migration, and metastasis, was conducted to assess the effect of NOD1. 
      C12-iE-DAP, a highly selective NOD1 ligand derived from gram-negative bacteria, 
      was used to activate NOD1. ML130, a specific NOD1 inhibitor, was used to block 
      C12-iE-DAP stimulation. Stable knockdown (KD) of NOD1 in human colon cancer cells 
      (HT29) was constructed with shRNA lentiviral transduction and the functional 
      assays were thus repeated. Lastly, the predominant signaling pathway of 
      NOD1-activation was identified using WB and functional assays in the presence of 
      specific kinase inhibitors. Our data demonstrate that NOD1 is highly expressed in 
      human colorectal cancer (CRC) and human and murine CRC cell lines. Clinically, we 
      demonstrate that this increased NOD1 expression negatively impacts survival in 
      patients with CRC. Subsequently, we identify NOD1 activation by C12-iE-DAP 
      augments CRC cell adhesion, migration and metastasis. These effects are 
      predominantly mediated via the p38 mitogen activated protein kinase (MAPK) 
      pathway. This is the first study implicating NOD1 in cancer metastasis, and thus 
      identifying this receptor as a putative therapeutic target.
FAU - Jiang, Henry Y
AU  - Jiang HY
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
AD  - Department of Experimental Surgery and Department of Surgery, McGill University, 
      1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
FAU - Najmeh, Sara
AU  - Najmeh S
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
AD  - Department of Experimental Surgery and Department of Surgery, McGill University, 
      1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
FAU - Martel, Guy
AU  - Martel G
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Centre, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada.
FAU - MacFadden-Murphy, Elyse
AU  - MacFadden-Murphy E
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Centre, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada.
FAU - Farias, Raquel
AU  - Farias R
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Centre, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada.
FAU - Savage, Paul
AU  - Savage P
AD  - The Rosalind and Morris Goodman Cancer Research Centre, McGill University, 1160 
      Pine Avenue, Montreal, QC, H3A 1A3, Canada.
FAU - Leone, Arielle
AU  - Leone A
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
AD  - Department of Experimental Surgery and Department of Surgery, McGill University, 
      1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
FAU - Roussel, Lucie
AU  - Roussel L
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Centre, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada.
FAU - Cools-Lartigue, Jonathan
AU  - Cools-Lartigue J
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
AD  - Department of Experimental Surgery and Department of Surgery, McGill University, 
      1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
FAU - Gowing, Stephen
AU  - Gowing S
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
AD  - Department of Experimental Surgery and Department of Surgery, McGill University, 
      1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
FAU - Berube, Julie
AU  - Berube J
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Centre, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada.
FAU - Giannias, Betty
AU  - Giannias B
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
FAU - Bourdeau, France
AU  - Bourdeau F
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
FAU - Chan, Carlos H F
AU  - Chan CHF
AD  - Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, 
      University of Iowa, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 
      Iowa City, IA, 52242, USA.
FAU - Spicer, Jonathan D
AU  - Spicer JD
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada.
AD  - Department of Experimental Surgery and Department of Surgery, McGill University, 
      1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
FAU - McClure, Rebecca
AU  - McClure R
AD  - Department of Pathology, Health Sciences North, 41 Ramsey Lake Road, Sudbury, ON, 
      Canada.
FAU - Park, Morag
AU  - Park M
AD  - The Rosalind and Morris Goodman Cancer Research Centre, McGill University, 1160 
      Pine Avenue, Montreal, QC, H3A 1A3, Canada.
FAU - Rousseau, Simon
AU  - Rousseau S
AD  - Meakins-Christie Laboratories, Research Institute of McGill University Health 
      Centre, 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada.
FAU - Ferri, Lorenzo E
AU  - Ferri LE
AD  - Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill 
      University Health Centre, 1001 Decarie Boulevard, Block E, Lab #E02-4134, 
      Montreal, QC, H4A 3J1, Canada. lorenzo.ferri@mcgill.ca.
AD  - Department of Experimental Surgery and Department of Surgery, McGill University, 
      1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. lorenzo.ferri@mcgill.ca.
LA  - eng
GR  - P30 CA086862/CA/NCI NIH HHS/United States
GR  - 8008959/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200119
PL  - Germany
TA  - Protein Cell
JT  - Protein & cell
JID - 101532368
RN  - 0 (NOD1 protein, human)
RN  - 0 (Nod1 Signaling Adaptor Protein)
RN  - 0 (Nod1 protein, mouse)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adenocarcinoma/*metabolism/pathology
MH  - Animals
MH  - Cell Adhesion
MH  - Cell Line
MH  - Cell Movement
MH  - Colonic Neoplasms/*metabolism/pathology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Metastasis
MH  - Nod1 Signaling Adaptor Protein/*physiology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC7026222
OTO - NOTNLM
OT  - ML130
OT  - NOD1
OT  - cancer migration
OT  - cancer-extracellular matrix adhesion
OT  - colon cancer
OT  - iE-DAP
OT  - intravital microscopy
OT  - metastasis
OT  - p38 MAPK activation
OT  - survival analysis
EDAT- 2020/01/21 06:00
MHDA- 2020/11/18 06:00
PMCR- 2020/01/19
CRDT- 2020/01/21 06:00
PHST- 2019/09/06 00:00 [received]
PHST- 2019/12/13 00:00 [accepted]
PHST- 2020/01/21 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2020/01/21 06:00 [entrez]
PHST- 2020/01/19 00:00 [pmc-release]
AID - 10.1007/s13238-019-00687-5 [pii]
AID - 687 [pii]
AID - 10.1007/s13238-019-00687-5 [doi]
PST - ppublish
SO  - Protein Cell. 2020 Mar;11(3):187-201. doi: 10.1007/s13238-019-00687-5. Epub 2020 
      Jan 19.