Skip to main content
SpringerLink
Log in

Effects of estrogen-related receptor alpha (ERRα) on proliferation and metastasis of human lung cancer A549 cells

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

Estrogen-related receptor alpha (ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790 (an inverse agonist of ERRα) were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 (CCK-8) and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1), the mesenchymal markers fibronectin (FN) and vimentin (Vim) and the transcription factors (Snail, Zeb1 Twist and Slug) were further detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition (EMT) of A549 cells, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Giguere V, Yang N, Segui P, et al. Identification of a new class of steroid hormone receptors. Nature, 1988,331(6151):91–94

    Article  CAS  PubMed  Google Scholar 

  2. Luo J, Sladek R, Carrier J, et al. Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha. Mol Cell Biol, 2003,23(22):7947–7956

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Shayu D, Rao AJ. Expression of functional aromatase in the epididymis: Role of androgens and LH in modulation of expression and activity. Mol Cell Endocrinol, 2006,249(1–2):40–50

    Article  CAS  PubMed  Google Scholar 

  4. Vanacker JM, Delmarre C, Guo X, et al. Activation of the osteopontin promoter by the orphan nuclear receptor estrogen receptor related alpha. Cell Growth Differ, 1998,9(12):1007–1014

    CAS  PubMed  Google Scholar 

  5. Dufour CR, Wilson BJ, Huss JM, et al. Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma. Cell Metab, 2007,5(5):345–356

    Article  CAS  PubMed  Google Scholar 

  6. Stein RA, McDonnell DP. Estrogen-related receptor alpha as a therapeutic target in cancer. Endocr-Relat Cancer, 2006,13:S25–S32

    Article  CAS  PubMed  Google Scholar 

  7. Ariazi EA, Kraus RJ, Farrell ML, et al. Estrogen-related receptor alpha1 transcriptional activities are regulated in part via the ErbB2/HER2 signaling pathway. Mol Cancer Res, 2007,5(1):71–85

    Article  CAS  PubMed  Google Scholar 

  8. Boudjadi S, Bernatchez G, Beaulieu JF, et al. Control of the human osteopontin promoter by ERRalpha in colorectal cancer. Am J Pathol, 2013,183(1):266–276

    Article  CAS  PubMed  Google Scholar 

  9. Lam SS, Mak AS, Yam JW, et al. Targeting estrogen-related receptor alpha inhibits epithelial-to-mesenchymal transition and stem cell properties of ovarian cancer cells. Mol Ther, 2014,22(4):743–751

    Article  CAS  PubMed  Google Scholar 

  10. Ariazi EA, Clark GM, Mertz JE. Estrogen-related receptor alpha and estrogen-related receptor gamma associate with unfavorable and favorable biomarkers, respectively, in human breast cancer. Cancer Res, 2002,62(22):6510–6518

    CAS  PubMed  Google Scholar 

  11. Fujimoto J, Alam SM, Jahan I, et al. Clinical implication of estrogen-related receptor (ERR) expression in ovarian cancers. J Steroid Biochem Mol Biol, 2007,104(3–5):301–304

    Article  CAS  PubMed  Google Scholar 

  12. Chang CY, Kazmin D, Jasper JS, et al. The metabolic regulator ERRalpha, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer. Cancer Cell, 2011,20(4):500–510

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Bernatchez G, Giroux V, Lassalle T, et al. ERRalpha metabolic nuclear receptor controls growth of colon cancer cells. Carcinogenesis, 2013,34(10):2253–2261

    Article  CAS  PubMed  Google Scholar 

  14. Eheman C, Henley SJ, Ballard-Barbash R, et al. Annual Report to the Nation on the status of cancer, 1975–2008, featuring cancers associated with excess weight and lack of sufficient physical activity. Cancer, 2012,118(9):2338–2366

    Article  PubMed  Google Scholar 

  15. Bouchardy C, Benhamou S, Schaffar R, et al. Lung cancer mortality risk among breast cancer patients treated with anti-estrogens. Cancer, 2011,117(6):1288–1295

    Article  PubMed  Google Scholar 

  16. Marquez-Garban DC, Chen HW, Fishbein MC, et al. Estrogen receptor signaling pathways in human non-small cell lung cancer. Steroids, 2007,72(2):135–143

    Article  CAS  PubMed  Google Scholar 

  17. Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009,139(5):871–890

    Article  CAS  PubMed  Google Scholar 

  18. Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta, 2009,1796(2):75–90

    CAS  PubMed  Google Scholar 

  19. Cano A, Peinado H, Olmeda D. Snail, ZEB and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer, 2007,7(6):415–428

    Article  PubMed  Google Scholar 

  20. Marino M, Galluzzo P, Ascenzi P. Estrogen signaling multiple pathways to impact gene transcription. Curr Genomics, 2006,7(8):497–508

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Bianco S, Sailland J, Vanacker JM. ERRs and cancers: Effects on metabolism and on proliferation and migration capacities. J Steroid Biochem Mol Biol, 2012,130(3–5): 180–185

    Article  CAS  PubMed  Google Scholar 

  22. Fujimoto J, Sato E. Clinical implication of estrogen-related receptor (ERR) expression in uterine endometrial cancers. J Steroid Biochem Mol Biol, 2009,116(1–2):71–75

    Article  CAS  PubMed  Google Scholar 

  23. Cavallini A, Notarnicola M, Giannini R, et al. Oestrogen receptor-related receptor alpha (ERRalpha) and oestrogen receptors (ERalpha and ERbeta) exhibit different gene expression in human colorectal tumour progression. Eur J Cancer, 2005,41(10):1487–1494

    Article  CAS  PubMed  Google Scholar 

  24. Cheung CP, Yu S, Wong KB, et al. Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues. J Clin Endocrinol Metab, 2005,90(3):1830–1844

    Article  CAS  PubMed  Google Scholar 

  25. Suzuki T, Miki Y, Moriya T, et al. Estrogen-related receptor a in human breast carcinoma as a potent prognostic factor. Cancer Res, 2004,64(13):4670–4676

    Article  CAS  PubMed  Google Scholar 

  26. Wang J, Wang Y, Wong C. Oestrogen-related receptor alpha inverse agonist XCT-790 arrests A549 lung cancer cell population growth by inducing mitochondrial reactive oxygen species production. Cell Prolif, 2010,43(2):103–113

    Article  CAS  PubMed  Google Scholar 

  27. Bianco S, Lanvin O, Tribollet V, et al. Modulating estrogen receptor-related receptor-alpha activity inhibits cell proliferation. J Biol Chem, 2009,284(35):23286–23292

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Xu S, Zhuang X, Pan X, et al. 1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as orally bioavailable transcriptional function suppressors of estrogen-related receptor alpha. J Med Chem, 2013,56(11):4631–4640

    Article  CAS  PubMed  Google Scholar 

  29. Stein RA, Chang CY, Kazmin DA, et al. Estrogen-related receptor alpha is critical for the growth of estrogen receptor-negative breast cancer. Cancer Res, 2008,68(21): 8805–8812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol, 2006,7(2):131–142

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Jian-wei Huang  (黄建伟), Bao-zhang Guan  (管保章), Liang-hong Yin  (尹良红), Fan-na Liu  (刘璠娜), Bo Hu  (胡 波), Qi-yi Zheng  (郑绮宜), Fo-lan Li  (李佛兰), Ying-xue Zhong  (钟影雪) & Yu Chen  (陈 宇)

Authors
  1. Jian-wei Huang  (黄建伟)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bao-zhang Guan  (管保章)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liang-hong Yin  (尹良红)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fan-na Liu  (刘璠娜)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Hu  (胡 波)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qi-yi Zheng  (郑绮宜)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fo-lan Li  (李佛兰)
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ying-xue Zhong  (钟影雪)
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yu Chen  (陈 宇)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liang-hong Yin  (尹良红).

Additional information

The authors contributed equally to this work.

This project was supported by the Fundamental Research Funds of the Central Universities (No. 21613316).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, Jw., Guan, Bz., Yin, Lh. et al. Effects of estrogen-related receptor alpha (ERRα) on proliferation and metastasis of human lung cancer A549 cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 875–881 (2014). https://doi.org/10.1007/s11596-014-1367-0

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-014-1367-0

Key words

Search

Navigation