Abstract
Lipopolysaccharide significantly increased invasion, cell proliferation, and phospho-NF-κB p65 and phospho-IGF-1R protein, but decreased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 cells in SW480 and HT29 colorectal cancer cells. In contrast, NF-κB inhibitor exhibited a counteract effect of lipopolysaccharide. Transfection of Toll-like receptor 4 shRNA significantly decreased phospho-NF-κB p65 and phospho-IGF-1R protein levels, invasion, but significantly increased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 in SW480 and HT29 cells. In conclusion, inflammation inhibits klotho gene expression in colorectal cancer cells through activation of Toll-like receptor 4 /NF-κB signal pathway.
Similar content being viewed by others
References
Cancer-World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/
Colorectal Cancer Statistics (2017) CA: Cancer J Clin. https://doi.org/10.3322/caac.21395
American Cancer Society (2014) Colorectal cancer facts & figures 2014-2016. Atlanta, Ga: American Cancer Society
Terzić J, Grivennikov S, Karin E, Karin M (2010) Inflammation and colon cancer. Gastroenterology 138:2101–2114.e5
Viennois E, Chen F, Merlin D (2013) NF-κB pathway in colitis-associated cancers. Transl Gastrointest Cancer 2:21–29
Zhu QC, Gao RY, Wu W, Qin HL (2013) Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer. Asian Pac J Cancer Prev 14:2689–2698
Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ (2010) HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol 28:367–388
Zhang G, Ghosh S (2000) Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through toll-like receptors. J Endotoxin Res 6:453–457
Zhou X, Wang X (2015) Klotho: a novel biomarker for cancer. J Cancer Res Clin Oncol 141:961–969
Tang X, Wang Y, Fan Z, Ji G, Wang M, Lin J, Huang S, Meltzer SJ (2016) Klotho: a tumor suppressor and modulator of the Wnt/β-catenin pathway in human hepatocellular carcinoma. Lab Investig 96:197–205
Wang L, Wang X, Wang X, Jie P, Lu H, Zhang S, Lin X, Lam EK, Cui Y, Yu J, Jin H (2011) Klotho is silenced through promoter hypermethylation in gastric cancer. Am J Cancer Res 1:111–119
Xie B, Chen J, Liu B, Zhan J (2013) Klotho acts as a tumor suppressor in cancers. Pathol Oncol Res 19:611–617
Wu C, Lv C, Chen F, Ma X, Shao Y, Wang Q (2015) The function of miR-199a-5p/klotho regulating TLR4/NF-κB p65/NGAL pathways in rat mesangial cells cultured with high glucose and the mechanism. Mol Cell Endocrinol 417:84–93
Roy A, Srivastava M, Saqib U, Liu D, Faisal SM, Sugathan S, Bishnoi S, Baig MS (2016) Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways. Int Immunopharmacol 40:79–89
Liu B, Sun L, Liu Q, Gong C, Yao Y, Lv X, Lin L, Yao H, Su F, Li D, Zeng M, Song E (2015) A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. Cancer Cell 27:370–381
Xie B, Zhou J, Yuan L, Ren F, Liu DC, Li Q, Shu G (2013) Epigenetic silencing of klotho expression correlates with poor prognosis of human hepatocellular carcinoma. Hum Pathol 44:795–801
Xie B, Zhou J, Shu G, Liu DC, Zhou J, Chen J, Yuan L (2013) Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells: tumor suppressive role of klotho in gastric cancer. Cancer Cell Int 13:18
Shu G, Xie B, Ren F, Liu DC, Zhou J, Li Q, Chen J, Yuan L, Zhou J (2013) Restoration of klotho expression induces apoptosis and autophagy in hepatocellular carcinoma cells. Cell Oncol (Dordr) 36:121–129
Acknowledgements
This study was supported by the Postdoctoral Science Foundation of China (2016 M602416), National Natural Science Foundation of China (81704089), Postdoctoral Science Fund Special Grant of China (2017 T100603), 2016 Postdoctoral Researcher Daily Funding of Hunan Province (49), the Department of Education Key Project of Hunan Province (15A024), and Changsha City’s Outstanding Innovation Youth Training Program (kq 1707012).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
All authors declared no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Xie, B., Nie, S., Hu, G. et al. The Involvement of NF-κB/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion. Pathol. Oncol. Res. 25, 1553–1565 (2019). https://doi.org/10.1007/s12253-018-0493-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12253-018-0493-6