Skip to main content

Advertisement

SpringerLink
Log in

TGF-β1 mediates estrogen receptor-induced epithelial-to-mesenchymal transition in some tumor lines

  • Research Article
  • Published:
Tumor Biology

Abstract

More and more studies have reported that epithelial-mesenchymal transition (EMT) involved in the process of cancer development and progression occurs. The EMT also plays an important role in the movement and transfer of the tumors. Transforming growth factor-β (TGF-β) could induce the EMT in some cancer cell types. However, the mechanism underlying this transition process has also not been entirely clarified. In this study, the results indicated that TGF-β1-mediated EMT in the tumor was associated with the estrogen receptor (ER). The decreased expression of vimentin and snail resulted in the decrease of the ER expression by small interfering RNA-mediated silencing and preventing the TGF-β-induced EMT. In conclusion, our results indicated that TGF-β1 is an estrogen receptor signaling and essential novel downstream targets and could act as an important factor in the TGF-β-induced EMT.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Zheng J, Li C, Wu X, Yang Y, Hao M, Sheng S, et al. Astrocyte elevated gene-1 is a novel biomarker of epithelial-mesenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumor Biol. 2014;35(3):2265–9.

    Article  CAS  Google Scholar 

  2. Lue HW, Yang X, Wang R, Qian W, Xu RZ, Lyles R, et al. LIV-1 promotes prostate cancer epithelial-to-mesenchymal transition and metastasis through HB-EGF shedding and EGFR-mediated ERK signaling. PLoS One. 2011;6(11):e27720.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Di Cello F, Li H, Vecchio-Pagán B, Gordon B, Harbom K, Shin J, et al. Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells. Mol Cancer. 2013;12(1):90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Vervoort SJ, Lourenco AR, van Boxtel R, Coffer PJ. SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition. PLoS One. 2013;8(1):e53238.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Lenferink AEG, Cantin C, Nantel A, Wang E, Durocher Y, Banville M, et al. Transcriptome profiling of a TGF-β-induced epithelial-to-mesenchymal transition reveals extracellular clusterin as a target for therapeutic antibodies. Oncogene. 2010;29(6):831–44.

    Article  CAS  PubMed  Google Scholar 

  6. Balanis N, Wendt MK, Schiemann BJ, Wang Z, Schiemann WP, Carlin CR. Epithelial to mesenchymal transition promotes breast cancer progression via a fibronectin-dependent STAT3 signaling pathway. J Biol Chem. 2013;288(25):17954–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Mak P, Chang C, Pursell B, Mercurio AM. Estrogen receptor β sustains epithelial differentiation by regulating prolyl hydroxylase 2 transcription. Proc Natl Acad Sci U S A. 2013;110(12):4708–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Lam SS, Mak AS, Yam JW, Cheung AN, Ngan HY, Wong AS. Targeting estrogen-related receptor alpha inhibits epithelial-to-mesenchymal transition and stem cell properties of ovarian cancer cells. Mol Ther. 2014;22(4):743–51.

    Article  CAS  PubMed  Google Scholar 

  9. Shao R, Shi J, Liu H, Shi X, Du X, Klocker H, et al. Epithelial-to-mesenchymal transition and estrogen receptor alpha mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia. Prostate. 2014;74(9):970–82.

    Article  CAS  PubMed  Google Scholar 

  10. Asiedu MK, Ingle JN, Behrens MD, Radisky DC, Knutson KL. TGFβ/TNFα-mediated epithelial–mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype. Cancer Res. 2011;71(13):4707–19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Romagnoli M, Belguise K, Yu Z, Wang X, Landesman-Bollag E, Seldin DC, et al. Epithelial-to-mesenchymal transition induced by TGF-β1 is mediated by Blimp-1–dependent repression of BMP-5. Cancer Res. 2012;72(23):6268–78.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Chua KN, Poon KL, Lim J, Sim WJ, Huang RYJ, Thiery JP. Target cell movement in tumor and cardiovascular diseases based on the epithelial–mesenchymal transition concept. Adv Drug Deliver Rev. 2011;63(8):558–67.

    Article  CAS  Google Scholar 

  13. Xu K, Wang X, Shi Q, Chen C, Tian C, Li XL, et al. Human prion protein mutants with deleted and inserted octarepeats undergo different pathways to trigger cell apoptosis. J Mol Neurosci. 2011;43(3):225–34.

    Article  CAS  PubMed  Google Scholar 

  14. Takebe N, Warren RQ, Ivy SP. Breast cancer growth and metastasis: interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition. Breast Cancer Res. 2011;13(3):211.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Farabaugh SM, Micalizzi DS, Jedlicka P, Zhao R, Ford HL. Eya2 is required to mediate the pro-metastatic functions of Six1 via the induction of TGF-β signaling, epithelial–mesenchymal transition, and cancer stem cell properties. Oncogene. 2012;31(5):552–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Wik E, Ræder MB, Krakstad C, Trovik J, Birkeland E, Hoivik EA, et al. Lack of estrogen receptor-α is associated with epithelial–mesenchymal transition and PI3K alterations in endometrial carcinoma. Clin Cancer Res. 2013;19(5):1094–105.

    Article  CAS  PubMed  Google Scholar 

  17. Stadler SC, Vincent CT, Fedorov VD, Patsialou A, Cherrington BD, Wakshlag JJ, et al. Dysregulation of PAD4-mediated citrullination of nuclear GSK3β activates TGF-β signaling and induces epithelial-to-mesenchymal transition in breast cancer cells. Proc Natl Acad Sci U S A. 2013;110(29):11851–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Stankic M, Pavlovic S, Chin Y, Brogi E, Padua D, Norton L, et al. TGF-β-Id1 signaling opposes Twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition. Cell Rep. 2013;5(5):1228–42.

    Article  CAS  PubMed  Google Scholar 

  19. Sivadas VP, Kannan S. The microRNA networks of TGF-beta signaling in cancer. Tumor Biol. 2014;35(4):1857–2869.

    Article  Google Scholar 

  20. Azhar M, Runyan RB, Gard C, Sanford LP, Miller ML, Andringa A, et al. Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development. Dv Cyn. 2009;238(2):431–42.

    CAS  Google Scholar 

  21. Medici D, Hay ED, Olsen BR. Snail and slug promote epithelial-mesenchymal transition through beta-catenin T cell factor-4-dependent expression of transforming growth factor-beta 3. Mol Bil Cell. 2008;19(1):4875–87.

    Article  CAS  Google Scholar 

  22. Yu Y, Xiao CH, Tan LD, Wang QS, Li XQ, Feng YM. Cancer-associated fibroblast induce epithelial-mesenchymal transition of breast cells through paracrine TGF-β signaling. Br J Cancer. 2014;110(3):724–32.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The present study was financially granted by the projects of Henan Health Bureau (ID. 201203077)

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Gynecology, The 1st Affiliated Hospital of He’nan University of Science and Technology, LuoYang, 471003, People’s Republic of China

    Dong-Mei Fan, Peng-Wei Qi, Ya-Wei Chen & Xiao-Lin Cheng

  2. Department of Oncology, The 1st Affiliated Hospital of He’nan University of Science and Technology, LuoYang, 471003, People’s Republic of China

    She-Gan Gao

Authors
  1. Dong-Mei Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peng-Wei Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. She-Gan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ya-Wei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-Lin Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to She-Gan Gao.

Additional information

Dong-Mei Fan and Peng-Wei Qi contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fan, DM., Qi, PW., Gao, SG. et al. TGF-β1 mediates estrogen receptor-induced epithelial-to-mesenchymal transition in some tumor lines. Tumor Biol. 35, 11277–11282 (2014). https://doi.org/10.1007/s13277-014-2166-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2166-8

Keywords

Search

Navigation