Advertisement

The Involvement of NF-κB/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion

  • Biao Xie
  • Shaolin Nie
  • Gui Hu
  • Li Xiong
  • Fan Hu
  • Mei Li
  • Tianshu Peng
  • Jing Nie
  • Yongheng He
Original Article
  • 27 Downloads

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.

Keywords

LPS NF-κB Colorectal cancer Klotho 

Notes

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).

Compliance with Ethical Standards

Conflict of Interest

All authors declared no conflict of interest.

References

  1. 1.
    Cancer-World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/
  2. 2.
    Colorectal Cancer Statistics (2017) CA: Cancer J Clin.  https://doi.org/10.3322/caac.21395 CrossRefGoogle Scholar
  3. 3.
    American Cancer Society (2014) Colorectal cancer facts & figures 2014-2016. Atlanta, Ga: American Cancer SocietyGoogle Scholar
  4. 4.
    Terzić J, Grivennikov S, Karin E, Karin M (2010) Inflammation and colon cancer. Gastroenterology 138:2101–2114.e5CrossRefGoogle Scholar
  5. 5.
    Viennois E, Chen F, Merlin D (2013) NF-κB pathway in colitis-associated cancers. Transl Gastrointest Cancer 2:21–29PubMedPubMedCentralGoogle Scholar
  6. 6.
    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 14:2689–2698CrossRefGoogle Scholar
  7. 7.
    Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ (2010) HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol 28:367–388CrossRefGoogle Scholar
  8. 8.
    Zhang G, Ghosh S (2000) Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through toll-like receptors. J Endotoxin Res 6:453–457CrossRefGoogle Scholar
  9. 9.
    Zhou X, Wang X (2015) Klotho: a novel biomarker for cancer. J Cancer Res Clin Oncol 141:961–969CrossRefGoogle Scholar
  10. 10.
    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 96:197–205CrossRefGoogle Scholar
  11. 11.
    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 1:111–119PubMedGoogle Scholar
  12. 12.
    Xie B, Chen J, Liu B, Zhan J (2013) Klotho acts as a tumor suppressor in cancers. Pathol Oncol Res 19:611–617CrossRefGoogle Scholar
  13. 13.
    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 417:84–93CrossRefGoogle Scholar
  14. 14.
    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 40:79–89CrossRefGoogle Scholar
  15. 15.
    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 27:370–381CrossRefGoogle Scholar
  16. 16.
    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 44:795–801CrossRefGoogle Scholar
  17. 17.
    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 13:18CrossRefGoogle Scholar
  18. 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) 36:121–129CrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  • Biao Xie
    • 1
  • Shaolin Nie
    • 2
  • Gui Hu
    • 3
  • Li Xiong
    • 4
  • Fan Hu
    • 1
  • Mei Li
    • 1
  • Tianshu Peng
    • 5
  • Jing Nie
    • 6
  • Yongheng He
    • 1
  1. 1.Department One of Anorectal SurgeryThe Second Affiliated Hospital of Hunan University of Chinese MedicineChangshaPeople’s Republic of China
  2. 2.Department of Colorectal SurgeryHunan Province Tumor HospitalChangshaChina
  3. 3.Department of Gastrointestinal Surgery, The Third Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.Department of Hepatobiliary Surgery, the Second Xiangya HospitalCentral South UniversityChangshaChina
  5. 5.Hunan Slack King Laboratory Animal Co., Ltd.ChangshaChina
  6. 6.Department Four of Anorectal SurgeryThe Second Affiliated Hospital of Hunan University of Chinese MedicineChangshaPeople’s Republic of China

Personalised recommendations