Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis
Received date: 06 Sep 2019
Accepted date: 13 Dec 2019
Published date: 15 Mar 2020
Copyright
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.
Henry Y. Jiang , Sara Najmeh , Guy Martel , Elyse MacFadden-Murphy , Raquel Farias , Paul Savage , Arielle Leone , Lucie Roussel , Jonathan Cools-Lartigue , Stephen Gowing , Julie Berube , Betty Giannias , France Bourdeau , Carlos H. F. Chan , Jonathan D. Spicer , Rebecca McClure , Morag Park , Simon Rousseau , Lorenzo E. Ferri . Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis[J]. Protein & Cell, 2020 , 11(3) : 187 -201 . DOI: 10.1007/s13238-019-00687-5
1 |
Anaya J (2016) OncoLnc: linking TCGA survival data to mRNAs, miRNAs, and lncRNAs. PeerJ Comput Sci 2:e67
|
2 |
Andalib A, Ramana-Kumar AV, Bartlett G, Franco EL, Ferri LE (2013) Influence of postoperative infectious complications on long-term survival of lung cancer patients: a population-based cohort study. J Thorac Oncol 8(5):554–561
|
3 |
Benko S,Tozser J, Miklossy G, Varga A, Kadas J, Csutak A, Berta A, Rajnavolgyi E (2008) Constitutive and UV-B modulated transcription of Nod-like receptors and their functional partners in human corneal epithelial cells. Mol Vis 14:1575–1583
|
4 |
Berube J,Bourdon C,Yao Y,Rousseau S (2009) Distinct intracellular signaling pathways control the synthesis of IL-8 and RANTES in TLR1/TLR2, TLR3 or NOD1 activated human airway epithelial cells. Cell Signal 21(3):448–456
|
5 |
Campbell NE, Kellenberger L,Greenaway J, Moorehead RA, Linnerth-Petrik NM, Petrik J(2010) Extracellular matrix proteins and tumor angiogenesis. J Oncol 2010:586905
|
6 |
Cario E (2013) The human TLR4 variant D299G mediates inflammation-associated cancer progression in the intestinal epithelium. Oncoimmunology 2(7):e24890
|
7 |
Carneiro LA, Travassos LH, Philpott DJ (2004) Innate immune recognition of microbes through Nod1 and Nod2: implications for disease. Microbes Infect 6(6):609–616
|
8 |
Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B, Bourdeau F, Kubes P, Ferri L (2013) Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest 123(8):3446–3458
|
9 |
Correa RG, Milutinovic S, Reed JC (2012) Roles of NOD1 (NLRC1) and NOD2 (NLRC2) in innate immunity and inflammatory diseases. Biosci Rep 32(6):597–608
|
10 |
del BarcoBarrantes I,Nebreda AR (2012) Roles of p38 MAPKs in invasion and metastasis. Biochem Soc Trans 40(1):79–84
|
11 |
Feng Y, Nie L, Thakur MD, Su Q, Chi Z, Zhao Y, Longmore GD (2010) A multifunctional lentiviral-based gene knockdown with concurrent rescue that controls for off-target effects of RNAi. Genomics Proteomics Bioinform 8(4):238–245
|
12 |
Girardin SE, Tournebize R, Mavris M, Page AL, Li X, Stark GR, Bertin J, DiStefano PS, Yaniv M, Sansonetti PJ
|
13 |
Haggar FA, Boushey RP (2009) Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 22(4):191–197
|
14 |
Han J, Lee JD, Tobias PS, Ulevitch RJ (1993) Endotoxin induces rapid protein tyrosine phosphorylation in 70Z/3 cells expressing CD14. J Biol Chem 268(33):25009–25014
|
15 |
Hou JM, Krebs M, Ward T, Sloane R, Priest L, Hughes A, Clack G, Ranson M, Blackhall F, Dive C (2011) Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol 178 (3):989–996
|
16 |
Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, Ferri LE (2011) LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res 71(5):1989–1998
|
17 |
Kang MJ, Heo SK, Song EJ, Kim DJ, Han SY, Han JH, Kim BY, Park JH (2012) Activation of Nod1 and Nod2 induces innate immune responses of prostate epithelial cells. Prostate 72(12):1351–1358
|
18 |
Kim S, Karin M (2011) Role of TLR2-dependent inflammation in metastatic progression. Ann N Y Acad Sci 1217:191–206
|
19 |
Kobayashi K, Inohara N, Hernandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R, Flavell RA (2002) RICK/Rip2/ CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416(6877):194–199
|
20 |
Koch M, Weitz J, Kienle P,Benner A,Willeke F,Lehnert T, Herfarth C, von Knebel Doeberitz M (2001) Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer. Arch Surg 136(1):85–89
|
21 |
Kramer RH, Gonzalez R, Nicolson GL (1980) Metastatic tumor cells adhere preferentially to the extracellular matrix underlying vascular endothelial cells. Int J Cancer 26(5):639–645
|
22 |
Lappas M (2013) NOD1 and NOD2 regulate proinflammatory and prolabor mediators in human fetal membranes and myometrium via nuclear factor-kappa B. Biol Reprod 89(1):14
|
23 |
Law WL, Choi HK, Lee YM, Ho JW, Seto CL (2007) Anastomotic leakage is associated with poor long-term outcome in patients after curative colorectal resection for malignancy. J Gastrointest Surg 1 1(1):8–15
|
24 |
Liu HM, Wang DL, Liu CY (1990) Interactions between fibrin, collagen and endothelial cells in angiogenesis. Adv Exp Med Biol 281:319–331
|
25 |
Matsui K, Horiuchi S, Sando S, Sera T, Aoyama Y(2006) RNAi silencing of exogenous and endogenous reporter genes using a macrocyclic octaamine as a “compact” siRNA carrier. Studies on the nonsilenced residual activity. Bioconjug Chem 17(1):132–138
|
26 |
Millrud CR, Kvarnhammar AM, Tajti J, Munck-Wikland E, Uddman R, Cardell LO (2013) Nod-like receptors in head and neck squamous cell carcinoma. Acta Otolaryngol 133(12):1333–1344
|
27 |
Ogura Y,Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G(2001) Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 276 (7):4812–4818
|
28 |
Ozbayer C, Kurt H, Bayramoglu A, Gunes HV, Metintas M, Degirmenci I,Oner KS (2015) The role of NOD1/CARD4 and NOD2/CARD15 genetic variations in lung cancer risk. Inflamm Res 64(10):775–779
|
29 |
Papavasiliou P, Fisher T,Kuhn J, Nemunaitis J, Lamont J (2010) Circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer. Proc (Bayl Univ Med Cent) 23 (1):11–14
|
30 |
Richmond A, Su Y (2008) Mouse xenograft models vs GEM models for human cancer therapeutics. Dis Model Mech 1(2–3):78–82
|
31 |
Ryschich E, Khamidjanov A, Kerkadze V,Buchler MW, Zoller M, Schmidt J (2009) Promotion of tumor cell migration by extracellular matrix proteins in human pancreatic cancer. Pancreas 38 (7):804–810
|
32 |
Schietroma M, Piccione F, Carlei F, Sista F, Cecilia EM, Amicucci G (2013) Peritonitis from perforated peptic ulcer and immune response. J Invest Surg 26(5):294–304
|
33 |
Sista F,Schietroma M, Santis GD, Mattei A,Cecilia EM, Piccione F, Leardi S, Carlei F, Amicucci G (2013) Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis. World J Gastrointest Surg 5(4):73–82
|
34 |
Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B, Kubes P, Ferri LE (2012) Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res 72(16):3919–3927
|
35 |
Wada T, Penninger JM (2004) Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23(16):2838–2849
|
36 |
Wang P, Zhang L, Jiang JM, Ma D, Tao HX, Yuan SL, Wang YC, Wang LC, Liang H,Zhang ZS
|
37 |
Wang X, Jiang W, Duan N, Qian Y,Zhou Q, Ye P,Jiang H, Bai Y, Zhang W, Wang W (2014) NOD1, RIP2 and Caspase12 are potentially novel biomarkers for oral squamous cell carcinoma development and progression. Int J Clin Exp Pathol 7(4):1677–1686
|
38 |
Weitz J, Koch M, Kienle P, Schrodel A, Willeke F, Benner A, Lehnert T, Herfarth C, von Knebel Doeberitz M (2000) Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer. Ann Surg 232 (1):66–72
|
39 |
Whelan MC, Senger DR (2003) Collagen I initiates endothelial cell morphogenesis by inducing actin polymerization through suppression of cyclic AMP and protein kinase A. J Biol Chem 278 (1):327–334
|
40 |
Zhang Y,Wu J, Xin Z, Wu X (2014) Aspergillus fumigatus triggers innate immune response via NOD1 signaling in human corneal epithelial cells. Exp Eye Res 127:170–178
|
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