Cell Biochemistry and Biophysics

, Volume 71, Issue 1, pp 465–472 | Cite as

BRMS1 Regulates Apoptosis in Non-small Cell Lung Cancer Cells

  • Jijun You
  • Xuejun He
  • Haibing Ding
  • Tingrong ZhangEmail author
Original Paper


Breast cancer metastasis suppressor 1 (BRMS1) was originally identified as a metastasis suppressor gene in human breast cancer. Previous studies have reported that loss of BRMS1 expression correlates with tumor progression, and poor prognosis in NSCLC. However, the role of BRMS1 in NSCLC is not fully understood. In this study, we found that expression of BRMS1 in A549 cells did not affect cell growth under normal culture conditions but sensitized cells to apoptosis induced by serum deprivation. Consistently, knockdown of endogenous BRMS1 expression in H1299 cells suppressed cell apoptosis. We identified that BRMS1 regulate apoptosis in NSCLC cells by modulating Stat3 activation. Taken together, our results show that BRMS1 sensitizes NSCLC cells to apoptosis through Stat3 signaling pathway, suggesting a potential role of BRMS1 in regulating NSCLC apoptosis and metastasis.


BRMS1 NSCLC Apoptosis Stat3 


  1. 1.
    Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: A Cancer Journal for Clinicians, 61(2), 69–90.Google Scholar
  2. 2.
    Govindan, R., Page, N., Morgensztern, D., Read, W., Tierney, R., Vlahiotis, A., et al. (2006). Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database. Journal of Clinical Oncology, 24(28), 4539–4544.PubMedCrossRefGoogle Scholar
  3. 3.
    Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Smigal, C., et al. (2006). Cancer statistics, 2006. CA: A Cancer Journal for Clinicians, 56(2), 106–130.Google Scholar
  4. 4.
    Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer, 2(8), 563–572.PubMedCrossRefGoogle Scholar
  5. 5.
    Germanov, E., Berman, J. N., & Guernsey, D. L. (2006). Current and future approaches for the therapeutic targeting of metastasis (review). International Journal of Molecular Medicine, 18(6), 1025–1036.PubMedGoogle Scholar
  6. 6.
    Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009). Cancer statistics, 2009. CA: A Cancer Journal for Clinicians, 59(4), 225–249.Google Scholar
  7. 7.
    Stafford, L. J., Vaidya, K. S., & Welch, D. R. (2008). Metastasis suppressors genes in cancer. The International Journal of Biochemistry & Cell Biology, 40(5), 874–891.CrossRefGoogle Scholar
  8. 8.
    Phillips, K. K., Welch, D. R., Miele, M. E., Lee, J. H., Wei, L. L., & Weissman, B. E. (1996). Suppression of MDA-MB-435 breast carcinoma cell metastasis following the introduction of human chromosome 11. Cancer Research, 56(6), 1222–1227.PubMedGoogle Scholar
  9. 9.
    Seraj, M. J., Samant, R. S., Verderame, M. F., & Welch, D. R. (2000). Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13. Cancer Research, 60(11), 2764–2769.PubMedGoogle Scholar
  10. 10.
    Shevde, L. A., Samant, R. S., Goldberg, S. F., Sikaneta, T., Alessandrini, A., Donahue, H. J., et al. (2002). Suppression of human melanoma metastasis by the metastasis suppressor gene, BRMS1. Experimental Cell Research, 273(2), 229–239.PubMedCrossRefGoogle Scholar
  11. 11.
    Zhang, S., Lin, Q. D., & Di, W. (2006). Suppression of human ovarian carcinoma metastasis by the metastasis-suppressor gene, BRMS1. International Journal of Gynecological Cancer, 16(2), 522–531.PubMedCrossRefGoogle Scholar
  12. 12.
    Jiang, J., Xia, M., Feng, J. B., & Kong, B. H. (2007). Inhibitory effect of breast cancer metastasis suppressor l gene on metastasis of human ovarian cancer cell in vitro and in vivo. Zhonghua fu chan ke za zhi, 42(6), 398–402.PubMedGoogle Scholar
  13. 13.
    Smith, P. W., Liu, Y., Siefert, S. A., Moskaluk, C. A., Petroni, G. R., & Jones, D. R. (2009). Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis and correlates with improved patient survival in non-small cell lung cancer. Cancer Letters, 276(2), 196–203.PubMedCrossRefGoogle Scholar
  14. 14.
    Samant, R. S., Seraj, M. J., Saunders, M. M., Sakamaki, T. S., Shevde, L. A., Harms, J. F., et al. (2000). Analysis of mechanisms underlying BRMS1 suppression of metastasis. Clinical & Experimental Metastasis, 18(8), 683–693.CrossRefGoogle Scholar
  15. 15.
    Liu, Y., Smith, P. W., & Jones, D. R. (2006). Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis. Molecular and Cellular Biology, 26(23), 8683–8696.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Wu, Y., Jiang, W., Wang, Y., Wu, J., Saiyin, H., Qiao, X., et al. (2012). Breast cancer metastasis suppressor 1 regulates hepatocellular carcinoma cell apoptosis via suppressing osteopontin expression. PLoS ONE, 7(8), e42976.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Qin, F. X., Shao, H. Y., Chen, X. C., Tan, S., Zhang, H. J., Miao, Z. Y., et al. (2011). Knockdown of NPM1 by RNA interference inhibits cells proliferation and induces apoptosis in leukemic cell line. International Journal of Medical Sciences, 8(4), 287–294.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Wang, Q., Qian, J., Wang, J., Luo, C., Chen, J., Hu, G., et al. (2013). Knockdown of RLIP76 expression by RNA interference inhibits invasion, induces cell cycle arrest, and increases chemosensitivity to the anticancer drug temozolomide in glioma cells. Journal of Neuro-oncology, 112(1), 73–82.PubMedCrossRefGoogle Scholar
  19. 19.
    Wang, J., Wang, Q., Cui, Y., Liu, Z. Y., Zhao, W., Wang, C. L., et al. (2012). Knockdown of cyclin D1 inhibits proliferation, induces apoptosis, and attenuates the invasive capacity of human glioblastoma cells. Journal of Neuro-oncology, 106(3), 473–484.PubMedCrossRefGoogle Scholar
  20. 20.
    Seki, Y., Suzuki, N., Imaizumi, M., Iwamoto, T., Usami, N., Ueda, Y., et al. (2004). STAT3 and MAPK in human lung cancer tissues and suppression of oncogenic growth by JAB and dominant negative STAT3. International Journal of Oncology, 24(4), 931–934.PubMedGoogle Scholar
  21. 21.
    Hurst, D. R., & Welch, D. R. (2011). Metastasis suppressor genes at the interface between the environment and tumor cell growth. International Review of Cell and Molecular Biology, 286, 107–180.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Yang, J., Zhang, B., Lin, Y., Yang, Y., Liu, X., & Lu, F. (2008). Breast cancer metastasis suppressor 1 inhibits SDF-1alpha-induced migration of non-small cell lung cancer by decreasing CXCR4 expression. Cancer Letters, 269(1), 46–56.PubMedCrossRefGoogle Scholar
  23. 23.
    Liu, Y., Mayo, M. W., Nagji, A. S., Hall, E. H., Shock, L. S., Xiao, A., et al. (2013). BRMS1 suppresses lung cancer metastases through an E3 ligase function on histone acetyltransferase p300. Cancer Research, 73(4), 1308–1317.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Hall, E. H., Liu, Y., Xiao, A., Shock, L., Brautigan, D. L., Mayo, M. W., et al. (2014). Inhibition of breast cancer metastasis suppressor 1 promotes a mesenchymal phenotype in lung epithelial cells that express oncogenic K-RasV12 and loss of p53. PLoS ONE, 9(4), e95869.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Simpson, C. D., Anyiwe, K., & Schimmer, A. D. (2008). Anoikis resistance and tumor metastasis. Cancer Letters, 272(2), 177–185.PubMedCrossRefGoogle Scholar
  26. 26.
    Decker, T., & Kovarik, P. (1999). Transcription factor activity of STAT proteins: structural requirements and regulation by phosphorylation and interacting proteins. Cellular and Molecular Life Sciences: CMLS, 55(12), 1535–1546.PubMedCrossRefGoogle Scholar
  27. 27.
    Yu, H., & Jove, R. (2004). The STATs of cancer—new molecular targets come of age. Nature Reviews Cancer, 4(2), 97–105.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jijun You
    • 1
  • Xuejun He
    • 2
  • Haibing Ding
    • 1
  • Tingrong Zhang
    • 3
    Email author
  1. 1.Department of Cardiothoracic SurgeryTaizhou Second People’s HospitalTaizhouChina
  2. 2.Department of OncologyTaizhou Second People’s HospitalTaizhouChina
  3. 3.Department of Oncology, The Affiliated Jiangyin People’s Hospital, School of MedicineSoutheast UniversityJiangyinChina

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