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Stanniocalcin-1 promotes metastasis in a human breast cancer cell line through activation of PI3K

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Abstract

Stanniocalcin-l (STC-1) is a secreted glycoprotein hormone that regulates calcium and phosphate homeostasis. STC-1 expression is upregulated in several cancers including breast cancer, and has been shown to be prognostic. Although these clinical observations implicate STC-1 as a potential tumor marker, it is still unclear whether STC-1 confers a malignant phenotype. In this study, this question was addressed by overexpressing STC-1 in the human breast cancer cell line MDA-MB-231 and examining the resultant phenotype in vitro and in vivo. Overexpression of STC-1 enhanced invasiveness of MDA-MB-231 cells in vitro and promoted their lung metastasis in vivo, while having no effect on proliferation, adhesion, or proteinase activity. The addition of soluble STC-1 to MDA-MB-231 cultures resulted in the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, suggesting a mechanistic basis for the observed increases in cell motility and metastasis. Taken together, it was indicated that secreted STC-1 promotes metastatic potential of breast cancer cells via activation of PI3K/AKT.

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Abbreviations

STC-1:

Stannocalcin-1

MAPK:

Mitogen-activated protein kinase

PI3K:

Phosphoinositide 3-kinase

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Acknowledgments

This study was supported by Grants-in-Aid for Scientific Research in Japan (Grant No. 24590700) M. T., K. K., D. K., and N. W.

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Authors and Affiliations

  1. Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan

    Ryosei Murai, Maki Tanaka, Yusuke Takahashi, Kageaki Kuribayashi, Daisuke Kobayashi & Naoki Watanabe

Authors
  1. Ryosei Murai
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  2. Maki Tanaka
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  3. Yusuke Takahashi
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  4. Kageaki Kuribayashi
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  5. Daisuke Kobayashi
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  6. Naoki Watanabe
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Corresponding author

Correspondence to Naoki Watanabe.

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Supplementary Figure 1

Real-time PCR and western blotting analysis of STC-1 expression in MDA-MB-231 breast cancer cell lines. (a) Transcript and (b) protein expression of STC-1 was detected by Real-time PCR and western blotting, respectively, in MB231-M and -S cells stably transfected with an empty control vector and a vector encoding secreted STC-1, respectively. Transcript expression was determined relative to the internal control GAPDH and Ran was used as a loading control for the western blotting. Supplementary material 1 (TIFF 19762 kb)

Supplementary Figure 2

The expression of phosphorylated Akt in MB231-M and -S cell lysates. Whole cell lysate from MB231-M and -S that cultured without FBS for 24 h was harvested. The level of phosphorylated Akt was detected by western blotting as described above. Supplementary material 2 (TIFF 19762 kb)

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Murai, R., Tanaka, M., Takahashi, Y. et al. Stanniocalcin-1 promotes metastasis in a human breast cancer cell line through activation of PI3K. Clin Exp Metastasis 31, 787–794 (2014). https://doi.org/10.1007/s10585-014-9668-z

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  • DOI: https://doi.org/10.1007/s10585-014-9668-z

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