Advertisement

Biotechnology Letters

, Volume 40, Issue 7, pp 1015–1027 | Cite as

BST2 promotes cell proliferation, migration and induces NF-κB activation in gastric cancer

  • Weiyu Liu
  • Yong Cao
  • Yadi Guan
  • Changqing Zheng
Original Research Paper
  • 161 Downloads

Abstract

Objectives

To investigate the functional roles of bone marrow stromal cell antigen 2 (BST2) in gastric cancer (GC) cells and its implications in the development of GC patients.

Results

BST2 was frequently overexpressed in GC tissues compared with the adjacent non-tumorous tissues, and high BST2 expression was correlated with tumor stage and lymphatic metastasis. Furthermore, in vitro experiments demonstrated that knockdown of BST2 by siRNA inhibited cell proliferation, induced apoptosis and repressed cell motility in GC cells. In addition, the pro-tumor function of BST2 in GC was mediated partly through the NF-κB signaling.

Conclusion

BST2 possesses the oncogenic potential in GC by regulating the proliferation, apoptosis, and migratory ability of GC cells, thereby BST2 could be a potential therapeutic target for the treatment of GC.

Keywords

BST2 Gastric cancer Proliferation Apoptosis NFκB 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. Bertuccio P et al (2009) Recent patterns in gastric cancer: a global overview. Int J Cancer 125:666–673.  https://doi.org/10.1002/ijc.24290 CrossRefPubMedGoogle Scholar
  2. Biswas DK, Shi Q, Baily S, Strickland I, Ghosh S, Pardee AB, Iglehart JD (2004) NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA 101:10137–10142.  https://doi.org/10.1073/pnas.0403621101 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cai D, Cao J, Li Z, Zheng X, Yao Y, Li W, Yuan Z (2009) Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis. BMC cancer 9:102.  https://doi.org/10.1186/1471-2407-9-102 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Chu D, Zhang Z, Li Y, Zheng J, Dong G, Wang W, Ji G (2011) Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer. Int J Cancer 129:887–895.  https://doi.org/10.1002/ijc.25734 CrossRefPubMedGoogle Scholar
  5. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656.  https://doi.org/10.1038/nrc883 CrossRefPubMedGoogle Scholar
  6. Cunningham D et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. New Engl J Med 355:11–20.  https://doi.org/10.1056/NEJMoa055531 CrossRefPubMedGoogle Scholar
  7. De Vita F et al (2014) Clinical management of advanced gastric cancer: the role of new molecular drugs. World J Gastroenterol 20:14537–14558.  https://doi.org/10.3748/wjg.v20.i40.14537 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Fan YZ, Zhao ZM, Fu JY, Chen CQ, Sun W (2010) Norcantharidin inhibits growth of human gallbladder carcinoma xenografted tumors in nude mice by inducing apoptosis and blocking the cell cycle in vivo. Hepatobiliary Pancreat Dis Int 9:414–422PubMedGoogle Scholar
  9. Fang KH et al (2014) Overexpression of BST2 is associated with nodal metastasis and poorer prognosis in oral cavity cancer. The Laryngoscope 124:E354–360.  https://doi.org/10.1002/lary.24700 CrossRefPubMedGoogle Scholar
  10. Ferlay J et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403.  https://doi.org/10.1016/j.ejca.2012.12.027 CrossRefPubMedGoogle Scholar
  11. Ferlay J et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–386.  https://doi.org/10.1002/ijc.29210 CrossRefPubMedGoogle Scholar
  12. Galao RP, Le Tortorec A, Pickering S, Kueck T, Neil SJ (2012) Innate sensing of HIV-1 assembly by Tetherin induces NFkappaB-dependent proinflammatory responses. Cell Host Microbe 12:633–644.  https://doi.org/10.1016/j.chom.2012.10.007 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Harada T, Ozaki S (2014) Targeted therapy for HM1.24 (CD317) on multiple myeloma cells. Biomed Res Int 2014:965384.  https://doi.org/10.1155/2014/965384 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hochegger H, Takeda S, Hunt T (2008) Cyclin-dependent kinases and cell-cycle transitions: does one fit all? Nat Rev Mol Cell Biol 9:910–916.  https://doi.org/10.1038/nrm2510 CrossRefPubMedGoogle Scholar
  15. Kanarek N, Ben-Neriah Y (2012) Regulation of NF-kappaB by ubiquitination and degradation of the IkappaBs. Immunol Rev 246:77–94.  https://doi.org/10.1111/j.1600-065X.2012.01098.x CrossRefPubMedGoogle Scholar
  16. Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 18:621–663.  https://doi.org/10.1146/annurev.immunol.18.1.621 CrossRefPubMedGoogle Scholar
  17. Kuang CM et al (2017) BST2 confers cisplatin resistance via NF-kappaB signaling in nasopharyngeal cancer. Cell Death Dis 8:e2874.  https://doi.org/10.1038/cddis.2017.271 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Kupzig S, Korolchuk V, Rollason R, Sugden A, Wilde A, Banting G (2003) Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic 4:694–709CrossRefPubMedGoogle Scholar
  19. Maeda S, Omata M (2008) Inflammation and cancer: role of nuclear factor-kappaB activation. Cancer Sci 99:836–842.  https://doi.org/10.1111/j.1349-7006.2008.00763.x CrossRefPubMedGoogle Scholar
  20. Mahauad-Fernandez WD, Okeoma CM (2016) The role of BST-2/Tetherin in host protection and disease manifestation. Immunity, inflammation and disease 4:4–23.  https://doi.org/10.1002/iid3.92 CrossRefPubMedGoogle Scholar
  21. Mahauad-Fernandez WD, DeMali KA, Olivier AK, Okeoma CM (2014) Bone marrow stromal antigen 2 expressed in cancer cells promotes mammary tumor growth and metastasis. Breast Cancer Res 16:493.  https://doi.org/10.1186/s13058-014-0493-8 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Marx J (1994) How Cells Cycle Toward Cancer. Science 263:319–321CrossRefPubMedGoogle Scholar
  23. Mukai S et al (2017) Overexpression of transmembrane protein BST2 is associated with poor survival of patients with esophageal, gastric, or colorectal cancer. Ann Surg Oncol 24:594–602.  https://doi.org/10.1245/s10434-016-5100-z CrossRefPubMedGoogle Scholar
  24. Neil SJ, Zang T, Bieniasz PD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425–430.  https://doi.org/10.1038/nature06553 CrossRefPubMedGoogle Scholar
  25. Ozaki S, Kosaka M, Wakatsuki S, Abe M, Koishihara Y, Matsumoto T (1997) Immunotherapy of multiple myeloma with a monoclonal antibody directed against a plasma cell-specific antigen, HM1.24. Blood 90:3179–3186PubMedGoogle Scholar
  26. Pham QT et al (2017) The expression of BTS-2 enhances cell growth and invasiveness in renal cell carcinoma. Anticancer Res 37:2853–2860.  https://doi.org/10.21873/anticanres.11637 PubMedCrossRefGoogle Scholar
  27. Qi S et al (2012) ZEB2 mediates multiple pathways regulating cell proliferation, migration, invasion, and apoptosis in glioma. PLoS ONE 7:e38842CrossRefPubMedPubMedCentralGoogle Scholar
  28. Sasaki N et al (2001) Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue. Clin Cancer Res 7:4136–4142PubMedGoogle Scholar
  29. Sherr CJ (1996) Cancer cell cycles Science 274:1672–1677PubMedGoogle Scholar
  30. Shigematsu Y et al (2017) Overexpression of the transmembrane protein BST-2 induces Akt and Erk phosphorylation in bladder cancer. Oncol Lett 14:999–1004.  https://doi.org/10.3892/ol.2017.6230 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Sokolova O, Naumann M (2017) NF-kappaB Signaling in Gastric Cancer Toxins 9  https://doi.org/10.3390/toxins9040119
  32. Tang Y, Lv P, Sun Z, Han L, Zhou W (2016) 14-3-3beta Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells by Modulating Expression of MMP2 and MMP9 through PI3 K/Akt/NF-kappaB Pathway. PLoS ONE 11:e0146070.  https://doi.org/10.1371/journal.pone.0146070 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Tokarev A, Suarez M, Kwan W, Fitzpatrick K, Singh R, Guatelli J (2013) Stimulation of NF-kappaB activity by the HIV restriction factor BST2. J Virol 87:2046–2057.  https://doi.org/10.1128/JVI.02272-12 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Vallabhapurapu S, Karin M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27:693–733.  https://doi.org/10.1146/annurev.immunol.021908.132641 CrossRefPubMedGoogle Scholar
  35. Velinov N, Poptodorov G, Gabrovski N, Gabrovski S (2010) The role of matrixmetalloproteinases in the tumor growth and metastasis. Khirurgiia 1:44–49Google Scholar
  36. Wang W et al (2009) HM1.24 (CD317) is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody. Cancer Immunol Immunother 58:967–976.  https://doi.org/10.1007/s00262-008-0612-4 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Weiyu Liu
    • 1
    • 2
  • Yong Cao
    • 1
  • Yadi Guan
    • 1
  • Changqing Zheng
    • 1
  1. 1.Department of GastroenterologyShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China
  2. 2.Department of GastroenterologyThe People’s Hospital of Liaoning ProvinceShenyangPeople’s Republic of China

Personalised recommendations