RETRACTED ARTICLE: Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation
- 11 April 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 114 (2), 251-262
- https://doi.org/10.1007/s10549-008-0009-2
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.Keywords
This publication has 56 references indexed in Scilit:
- Changes in Cytoskeletal Protein Composition Indicative of an Epithelial-Mesenchymal Transition in Human Micrometastatic and Primary Breast Carcinoma CellsClinical Cancer Research, 2005
- Wnt‐3a regulates chondrocyte differentiation via c‐Jun/AP‐1 pathwayFEBS Letters, 2005
- Invasion and Metastasis in Colorectal Cancer: Epithelial-Mesenchymal Transition, Mesenchymal-Epithelial Transition, Stem Cells and β-CateninCells Tissues Organs, 2005
- Cross-regulation of Wnt signaling and cell adhesionDifferentiation, 2004
- A role for MEK kinase 1 in TGF- /activin-induced epithelium movement and embryonic eyelid closureThe EMBO Journal, 2003
- Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulationGenes & Development, 2003
- The Wnt signalling pathwayJournal of Cell Science, 2002
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Glypicans: a growing trendNature Genetics, 1996
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976