Open Access

STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits

  • Authors:
    • Seyung S. Chung
    • Nolan Giehl
    • Yanyuan Wu
    • Jaydutt V. Vadgama
  • View Affiliations

  • Published online on: November 29, 2013     https://doi.org/10.3892/ijo.2013.2195
  • Pages: 403-411
  • Copyright: © Chung et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Clinically, HER2 proto-oncogene amplification is found in about 25-30% of human breast cancers, where it is correlated to a poor prognosis. Constitutive STAT3 activation is found in about 50-60% of the breast tumors and associated with tumorigenesis and drug resistance. In this study, we showed that STAT3 was phosphorylated in HER2-overexpressing, ER-positive human breast tumors and, furthermore, phosphorylated STAT3 promoted the stem-like cell phenotype. We examined the dysregulation of the stem cell markers (Oct-4, Sox-2 and CD44) and the tumorsphere formation in HER2-overexpressing human breast cancer cell lines. We demonstrated that the STAT3 inhibitor, Stattic, treatment abolished the cancer stem cell phenotype in HER2-positive breast cancers. Combined treatment of Herceptin and Stattic showed the synergistic effect on the cancer cell growth in vitro. In addition, when the STAT3 gene was knocked down, the expression of the stem cell markers Oct-4, Sox-2 and CD44 were downregulated and tumorsphere formation was abolished. HER2-elicited STAT3 signaling may provide a potential model for drug resistance induced by stem-like cell characteristics. This mechanism may be responsible for acquiring resistance to Herceptin in the treatment of HER2-overexpressing breast tumors. Based on our findings, targeting pSTAT3 could overcome Herceptin-induced resistance in HER2-overexpressing breast tumors.
View Figures
View References

Related Articles

Journal Cover

2014-February
Volume 44 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Chung SS, Giehl N, Wu Y and Vadgama JV: STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits. Int J Oncol 44: 403-411, 2014
APA
Chung, S.S., Giehl, N., Wu, Y., & Vadgama, J.V. (2014). STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits. International Journal of Oncology, 44, 403-411. https://doi.org/10.3892/ijo.2013.2195
MLA
Chung, S. S., Giehl, N., Wu, Y., Vadgama, J. V."STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits". International Journal of Oncology 44.2 (2014): 403-411.
Chicago
Chung, S. S., Giehl, N., Wu, Y., Vadgama, J. V."STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits". International Journal of Oncology 44, no. 2 (2014): 403-411. https://doi.org/10.3892/ijo.2013.2195