Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2009
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Resumo |
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. FONCyT (PICT)[14088] FONCyT (PICT) University of Buenos Aires, Argentina University of Buenos Aires[1728/OC-AR], Argentina Universidad de Buenos Aires UBACyT, Argentina Universidad de Buenos Aires UBACyT[M068], Argentina |
Identificador |
BREAST CANCER RESEARCH AND TREATMENT, v.114, n.2, p.251-262, 2009 0167-6806 http://producao.usp.br/handle/BDPI/30852 10.1007/s10549-008-0009-2 |
Idioma(s) |
eng |
Publicador |
SPRINGER |
Relação |
Breast Cancer Research and Treatment |
Direitos |
restrictedAccess Copyright SPRINGER |
Palavras-Chave | #beta-Catenin #Cell-cell adhesion #Cell migration #Cell survival #Cytoskeleton #E-Cadherin #Glypican-3 #JNK #Wnt signaling #EPITHELIAL-MESENCHYMAL TRANSITION #CONVERGENT EXTENSION MOVEMENTS #HEPARAN-SULFATE PROTEOGLYCANS #GOLABI-BEHMEL-SYNDROME #N-TERMINAL KINASE #HEPATOCELLULAR-CARCINOMA #GASTRULATION MOVEMENTS #BREAST-CANCER #BETA-CATENIN #PROTEIN #Oncology |
Tipo |
article original article publishedVersion |