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Differential role of psoriasin (S100A7) in estrogen receptor α positive and negative breast cancer cells occur through actin remodeling

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Abstract

Psoriasin (S100A7) is a calcium-binding protein that has shown to be highly expressed in high-grade ductal carcinoma in situ (DCIS) and a subset of invasive breast cancers. However, its role in invasion and metastasis is not very well known. In this study, we have shown that S100A7 differentially regulates epidermal growth factor (EGF)-induced cell migration and invasion in ERα− MDA-MB-231 cells and ERα+ MCF-7 and T47D breast cancer cells. Further signaling studies revealed that S100A7 enhances EGF-induced EGFR phosphorylation and actin remodeling that seems to favor lamellipodia formation in ERα− cells. In addition, S100A7 overexpression enhanced NF-κB-mediated matrix metalloproteinase-9 (MMP-9) secretion in MDA-MB-231 cells indicating its role in enhanced invasiveness. However, S100A7 overexpression inhibited migration and invasion of MCF-7 cells by inactivating Rac-1 pathway and MMP-9 secretion. Moreover, S100A7 overexpressing MDA-MB-231 cells showed enhanced metastasis compared to vector control in in vivo nude mice as detected by bioluminescence imaging. Our tissue microarray data also revealed predominant expression of S100A7 in ERα− metastatic carcinoma, especially in lymph node regions. Overall these studies suggest that S100A7 may enhance metastasis in ERα− breast cancer cells by a novel mechanism through regulation of actin cytoskeleton and MMP-9 secretion.

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Abbreviations

S100A7:

Psoriasin

ERα:

Estrogen receptor α

EGF:

Epidermal growth factor

DCIS:

Ductal carcinoma in situ

IHC:

Immunohistochemistry

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Acknowledgments

This work was supported in part by grants from National Institutes of Health (CA109527 and CA153490) and Department of Defense to R.K. Ganju. Y.S. Deol was supported by Pelotonia Fellowship from Comprehensive Cancer Center, The Ohio State University. Authors thank Dr. Zahida Qamri, Dr. Nandu Thodi and Mohamed Adel for their help in in vivo BLI imaging. We also thank Viy McGaughy for IHC staining.

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None.

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Authors and Affiliations

  1. Department of Pathology, The Ohio State University, Columbus, OH, 43210, USA

    Amita Sneh, Yadwinder S. Deol, Akaansha Ganju, Konstantin Shilo, Mohd W. Nasser & Ramesh K. Ganju

  2. Department of Veterinary Sciences, The Ohio State University, Columbus, OH, 43210, USA

    Thomas J. Rosol

  3. The Ohio State University, 840 Biomedical Research Tower, 460 W. 12th Avenue, Columbus, OH, 43210, USA

    Mohd W. Nasser

  4. The Ohio State University, 810 Biomedical Research Tower, 460 W. 12th Avenue, Columbus, OH, 43210, USA

    Ramesh K. Ganju

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  1. Amita Sneh
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  2. Yadwinder S. Deol
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Corresponding authors

Correspondence to Mohd W. Nasser or Ramesh K. Ganju.

Additional information

Amita Sneh and Yadwinder S. Deol contributed equally to this study.

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Sneh, A., Deol, Y.S., Ganju, A. et al. Differential role of psoriasin (S100A7) in estrogen receptor α positive and negative breast cancer cells occur through actin remodeling. Breast Cancer Res Treat 138, 727–739 (2013). https://doi.org/10.1007/s10549-013-2491-4

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