Journal article
Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis
Protein & cell, Vol.11(3), pp.187-201
03/01/2020
DOI: 10.1007/s13238-019-00687-5
PMCID: PMC7026222
PMID: 31956962
Abstract
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.
Details
- Title: Subtitle
- Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis
- Creators
- Henry Y. Jiang - McGill UniversitySara Najmeh - McGill UniversityGuy Martel - McGill University Health CentreElyse MacFadden-Murphy - McGill University Health CentreRaquel Farias - McGill University Health CentrePaul Savage - The Rosalind and Morris Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue, Montreal, QC, H3A 1A3, Canada.Arielle Leone - McGill UniversityLucie Roussel - McGill University Health CentreJonathan Cools-Lartigue - McGill UniversityStephen Gowing - McGill UniversityJulie Berube - McGill University Health CentreBetty Giannias - McGill University Health CentreFrance Bourdeau - McGill Univ, Res Inst, Thorac & Upper GI Canc Res Labs, Hlth Ctr, 1001 Decarie Blvd,Block E,Lab E02-4134, Montreal, PQ H4A 3J1, CanadaCarlos H. F. Chan - Roy J. and Lucille A. Carver College of MedicineJonathan D. Spicer - McGill UniversityRebecca McClure - Health Sciences NorthMorag Park - The Rosalind and Morris Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue, Montreal, QC, H3A 1A3, Canada.Simon Rousseau - McGill University Health CentreLorenzo E. Ferri - McGill University
- Resource Type
- Journal article
- Publication Details
- Protein & cell, Vol.11(3), pp.187-201
- DOI
- 10.1007/s13238-019-00687-5
- PMID
- 31956962
- PMCID
- PMC7026222
- NLM abbreviation
- Protein Cell
- ISSN
- 1674-800X
- eISSN
- 1674-8018
- Publisher
- Springer Nature
- Number of pages
- 15
- Grant note
- 8008959 / Canadian Institute of Health Research; Canadian Institutes of Health Research (CIHR)
- Language
- English
- Date published
- 03/01/2020
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984312982802771
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