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Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation

Breast Cancer Research and Treatment volume 114, pages 251–262 (2009)Cite this article

Abstract

Glypican-3 (GPC3) is a proteoglycan involved in migration, proliferation and cell survival modulation in several tissues. There are many reports demonstrating a downregulation of GPC3 expression in some human tumors, including mesothelioma, ovarian and breast cancer. Previously, we determined that GPC3 reexpression in the murine mammary adenocarcinoma LM3 cells induced an impairment of their in vivo invasive and metastatic capacities together with a higher susceptibility to in vitro apoptosis. Currently, the signaling mechanism of GPC3 is not clear. First, it was speculated that GPC3 regulates the insulin-like growth factor (IGF) signaling system. This hypothesis, however, has been strongly challenged. Recently, several reports indicated that at least in some cell types GPC3 serves as a selective regulator of Wnt signaling. Here we provide new data demonstrating that GPC3 regulates Wnt pathway in the metastatic adenocarcinoma mammary LM3 cell line. We found that GPC3 is able to inhibit canonical Wnt signals involved in cell proliferation and survival, as well as it is able to activate non canonical pathway, which directs cell morphology and migration. This is the first report indicating that breast tumor cell malignant properties can be reverted, at least in part, by GPC3 modulation of Wnt signaling. Our results are consistent with the potential role of GPC3 as a metastasis suppressor.

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Acknowledgements

The work was supported by grants from FONCyT (PICT 14088, Préstamo BID 1728/OC-AR) and from the University of Buenos Aires (UBACyT M068). We would like to give our thanks to Guillermo Peluffo for technical assistance.

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Affiliations

  1. Cell Biology Department, Research Area, Institute of Oncology “Angel H. Roffo”, University of Buenos Aires, Av. San Martín 5481 (C1417DTB), Buenos Aires, Argentina

    Ivan Stigliano, Lydia Puricelli, Elisa Bal de Kier Joffé & María Giselle Peters

  2. Molecular and Cellular Biology Research, Sunnybrook and Women′s College Health Science Center, University of Toronto, Toronto, ON, Canada, M4N3M5

    Jorge Filmus

  3. Chemistry Institute, University of São Paulo, São Paulo, 05508-900, Brazil

    Mari Cleide Sogayar

Authors
  1. Ivan Stigliano
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  2. Lydia Puricelli
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  3. Jorge Filmus
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  4. Mari Cleide Sogayar
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  5. Elisa Bal de Kier Joffé
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  6. María Giselle Peters
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Corresponding author

Correspondence to María Giselle Peters.

Additional information

Lydia Puricelli, Elisa Bal de Kier Joffé and María Giselle Peters are the members of the National Council of Scientific and Technical Research (CONICET).

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Stigliano, I., Puricelli, L., Filmus, J. et al. Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation. Breast Cancer Res Treat 114, 251–262 (2009). https://doi.org/10.1007/s10549-008-0009-2

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  • DOI: https://doi.org/10.1007/s10549-008-0009-2

Keywords

  • β-Catenin
  • Cell–cell adhesion
  • Cell migration
  • Cell survival
  • Cytoskeleton
  • E-Cadherin
  • Glypican-3
  • JNK
  • Wnt signaling