NADPH Oxidase 1-dependent ROS is Crucial for TLR4 Signaling to Promote Tumor Metastasis of Non-small Cell Lung Cancer

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2015 Jan 17

PMID 25592377

Citations 36

Authors

Xiyu Liu

Changyan Pei

Song Yan

Guifeng Liu

Gang Liu

Wenqing Chen

Youbin Cui

Yahui Liu

Affiliations

Soon will be listed here.

Abstract

Recent evidence demonstrated an enhanced metastasis of non-small cell lung cancer (NSCLC) cells induced by lipopolysaccharide (LPS) stimulation, which reflected an important role of inflammation in tumor progression. However, the underlying mechanisms still remain unclear. Here, we evaluated the potential role of reactive oxygen species (ROS) in Toll-like receptor 4 (TLR4) signaling enhanced NSCLC metastasis. NSCLC cells were isolated from clinical surgical tissues. We found that LPS stimulation of NSCLC cells facilitates their metastasis that was accompanied by increased ROS production and could be abrogated by ROS inhibition. NADPH oxidase was essential for TLR4 signaling-enhanced NSCLC metastasis. Elevated NADPH oxidase 1 (NOX1) expression by LPS stimulation was observed. Blockade of NOX1 with ML171 alleviated enhanced NSCLC metastasis by TLR4 signaling. Enforced NOX1 expression promoted TLR4 signaling-enhanced NSCLC metastasis, while decreased NOX1 expression inhibited TLR4 signaling-enhanced NSCLC metastasis. Further, NOX1 could regulate the expression of CXCR4 and matrix metallopeptidase 9 (MMP9) in NSCLC cells. NOX1 expression in tumor tissues was correlated with TLR4 expression and clinical stages in NSCLC patients. Finally, inhibition of NOX1/ROS prevented enhanced lung tumor burdens of NSCLC by LPS-induced acute lung infection. Our findings demonstrated a crucial role of NOX1-dependent ROS for TLR4 signaling to enhance the metastasis of NSCLC, which could further the understanding of NSCLC pathogenesis and helpful for developing novel therapeutics for NSCLC.

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References

Cattaneo F, Iaccio A, Guerra G, Montagnani S, Ammendola R . NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells. Free Radic Biol Med. 2011; 51(6):1126-36. DOI: 10.1016/j.freeradbiomed.2011.05.040. View

Komatsu D, Kato M, Nakayama J, Miyagawa S, Kamata T . NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression. Oncogene. 2008; 27(34):4724-32. DOI: 10.1038/onc.2008.102. View

Govindan R, Bogart J, Vokes E . Locally advanced non-small cell lung cancer: the past, present, and future. J Thorac Oncol. 2008; 3(8):917-28. DOI: 10.1097/JTO.0b013e318180270b. View

Li C, Li H, Jiang K, Li J, Gai X . TLR4 signaling pathway in mouse Lewis lung cancer cells promotes the expression of TGF-β1 and IL-10 and tumor cells migration. Biomed Mater Eng. 2013; 24(1):869-75. DOI: 10.3233/BME-130879. View

Suleiman A, Nogova L, Fuhr U . Modeling NSCLC progression: recent advances and opportunities available. AAPS J. 2013; 15(2):542-50. PMC: 3675755. DOI: 10.1208/s12248-013-9461-y. View

Coso S, Harrison I, Harrison C, Vinh A, Sobey C, Drummond G . NADPH oxidases as regulators of tumor angiogenesis: current and emerging concepts. Antioxid Redox Signal. 2012; 16(11):1229-47. DOI: 10.1089/ars.2011.4489. View

OLeary D, Bhatt L, Woolley J, Gough D, Wang J, Cotter T . TLR-4 signalling accelerates colon cancer cell adhesion via NF-κB mediated transcriptional up-regulation of Nox-1. PLoS One. 2012; 7(10):e44176. PMC: 3469572. DOI: 10.1371/journal.pone.0044176. View

Liao S, Zhou Y, Yuan Y, Li D, Wu F, Wang Q . Triggering of Toll-like receptor 4 on metastatic breast cancer cells promotes αvβ3-mediated adhesion and invasive migration. Breast Cancer Res Treat. 2011; 133(3):853-63. DOI: 10.1007/s10549-011-1844-0. View

Hsu R, Chan C, Spicer J, Rousseau M, Giannias B, Rousseau S . LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res. 2011; 71(5):1989-98. DOI: 10.1158/0008-5472.CAN-10-2833. View

10.

Li Q, Han Y, Fei G, Guo Z, Ren T, Liu Z . IL-17 promoted metastasis of non-small-cell lung cancer cells. Immunol Lett. 2012; 148(2):144-50. DOI: 10.1016/j.imlet.2012.10.011. View

11.

Wen Z, Xu L, Chen X, Xu W, Yin Z, Gao X . Autoantibody induction by DNA-containing immune complexes requires HMGB1 with the TLR2/microRNA-155 pathway. J Immunol. 2013; 190(11):5411-22. DOI: 10.4049/jimmunol.1203301. View

12.

Cheng S, Lee I, Lin C, Wu W, Hsiao L, Yang C . ATP mediates NADPH oxidase/ROS generation and COX-2/PGE2 expression in A549 cells: role of P2 receptor-dependent STAT3 activation. PLoS One. 2013; 8(1):e54125. PMC: 3543320. DOI: 10.1371/journal.pone.0054125. View

13.

Bedard K, Krause K . The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007; 87(1):245-313. DOI: 10.1152/physrev.00044.2005. View

14.

Zhang Y, He F, Fang M, Hua T, Hu B, Zhang Z . Increased expression of Toll-like receptors 4 and 9 in human lung cancer. Mol Biol Rep. 2008; 36(6):1475-81. DOI: 10.1007/s11033-008-9338-9. View

15.

Kim J, Yeo S, Shin D, Bae Y, Lee J, Chin B . Glycogen synthase kinase 3beta and beta-catenin pathway is involved in toll-like receptor 4-mediated NADPH oxidase 1 expression in macrophages. FEBS J. 2010; 277(13):2830-7. DOI: 10.1111/j.1742-4658.2010.07700.x. View

16.

Griffith B, Pendyala S, Hecker L, Lee P, Natarajan V, Thannickal V . NOX enzymes and pulmonary disease. Antioxid Redox Signal. 2009; 11(10):2505-16. PMC: 2821137. DOI: 10.1089/ars.2009.2599. View

17.

Pei J, Lou Y, Zhong R, Han B . MMP9 activation triggered by epidermal growth factor induced FoxO1 nuclear exclusion in non-small cell lung cancer. Tumour Biol. 2014; 35(7):6673-8. DOI: 10.1007/s13277-014-1850-z. View

18.

Laurent E, McCoy 3rd J, Macina R, Liu W, Cheng G, Robine S . Nox1 is over-expressed in human colon cancers and correlates with activating mutations in K-Ras. Int J Cancer. 2008; 123(1):100-7. PMC: 3774003. DOI: 10.1002/ijc.23423. View

19.

Jing Y, Han Z, Sun K, Zhang S, Hou J, Liu Y . Toll-like receptor 4 signaling promotes epithelial-mesenchymal transition in human hepatocellular carcinoma induced by lipopolysaccharide. BMC Med. 2012; 10:98. PMC: 3482562. DOI: 10.1186/1741-7015-10-98. View

20.

Kanne J . Screening for lung cancer: what have we learned?. AJR Am J Roentgenol. 2014; 202(3):530-5. DOI: 10.2214/AJR.13.11540. View