scholarly journals Loss of Transforming Growth Factor-β Signaling in Mammary Fibroblasts Enhances CCL2 Secretion to Promote Mammary Tumor Progression through Macrophage-Dependent and -Independent Mechanisms

Neoplasia ◽  
2010 ◽  
Vol 12 (5) ◽  
pp. 425-433 ◽  
Author(s):  
Stacey L. Hembruff ◽  
Iman Jokar ◽  
Li Yang ◽  
Nikki Cheng
Keyword(s):  
Growth Factor ◽  
Tumor Progression ◽  
Mammary Tumor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mammary Tumor Progression

scholarly journals Signaling through ShcA Is Required for Transforming Growth Factor β- and Neu/ErbB-2-Induced Breast Cancer Cell Motility and Invasion

2008 ◽  
Vol 28 (10) ◽  
pp. 3162-3176 ◽  
Author(s):  
Jason J. Northey ◽  
Juliann Chmielecki ◽  
Elaine Ngan ◽  
Caterina Russo ◽  
Matthew G. Annis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cell Motility ◽  
Cancer Cells ◽  
Mammary Tumor ◽  
Breast Cancer Cells ◽  
Transforming Growth Factor ◽  
Adaptor Protein ◽  
Transforming Growth Factor Β ◽  
Migration And Invasion

ABSTRACT Cooperation between the Neu/ErbB-2 and transforming growth factor β (TGF-β) signaling pathways enhances the invasive and metastatic capabilities of breast cancer cells; however, the underlying mechanisms mediating this synergy have yet to be fully explained. We demonstrate that TGF-β induces the migration and invasion of mammary tumor explants expressing an activated Neu/ErbB-2 receptor, which requires signaling from autophosphorylation sites located in the C terminus. A systematic analysis of mammary tumor explants expressing Neu/ErbB-2 add-back receptors that couple to distinct signaling molecules has mapped the synergistic effect of TGF-β-induced motility and invasion to signals emanating from tyrosine residues 1226/1227 and 1253 of Neu/ErbB-2. Given that the ShcA adaptor protein is known to interact with Neu/ErbB-2 through these residues, we investigated the importance of this signaling molecule in TGF-β-induced cell motility and invasion. The reduction of ShcA expression rendered cells expressing activated Neu/ErbB-2, or add-back receptors signaling specifically through tyrosines 1226/1227 or 1253, unresponsive to TGF-β-induced motility and invasion. In addition, a dominant-negative form of ShcA, lacking its three known tyrosine phosphorylation sites, completely abrogates the TGF-β-induced migration and invasion of breast cancer cells expressing activated Neu/ErbB-2. Our results implicate signaling through the ShcA adaptor as a key component in the synergistic interaction between these pathways.

scholarly journals Transforming Growth Factor β Enhances the Glucocorticoid Response of the Mouse Mammary Tumor Virus Promoter through Smad and GA-Binding Proteins

2004 ◽  
Vol 78 (5) ◽  
pp. 2201-2211 ◽  
Author(s):  
Koldo Aurrekoetxea-Hernández ◽  
Elena Buetti
Keyword(s):  
Growth Factor ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Regulatory Elements ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

ABSTRACT Tissue-specific transcription is advantageously investigated by using viral promoters, which are selected for compact regulatory elements. Mouse mammary tumor virus (MMTV) has adapted to specialized cell types and targets initially B lymphocytes. We previously showed that, in B-cell lines, glucocorticoid-induced MMTV transcription requires an ETS family factor, GA-binding protein (GABP), bound in tandem to the MMTV DNA next to the glucocorticoid receptor (GR). We now report that transforming growth factor β (TGF-β) superinduces this response up to 10-fold through binding of its effectors, Smads, between the GABP-binding motifs. The basal level was unaffected. The TGF-β-glucocorticoid cooperation also depended on GR and GABP binding, was transferable to another promoter, and occurred both with transiently transfected and with integrated templates. Smad3 associated in vitro with GR, with GABPα (via the MH2 domain), and with GABPβ, Smad4 only with GABPα. Interactions of Smad3 with GABP (when coexpressed or endogenous to B cells) were shown by coprecipitation and by mammalian two-hybrid assay. This composite DNA element integrates three signaling pathways deriving from TGF-β, glucocorticoid hormones, and a unique ETS factor, and may allow MMTV to exploit factors from the milk. It may as well indicate novel possibilities for cellular regulatory networks.

scholarly journals Targeting all transforming growth factor-β isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer

2020 ◽  
Vol 295 (36) ◽  
pp. 12559-12572
Author(s):  
Kazuki Takahashi ◽  
Yuichi Akatsu ◽  
Katarzyna A. Podyma-Inoue ◽  
Takehisa Matsumoto ◽  
Hitomi Takahashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Oral Cancer ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Oral Cancer Cells ◽  
Tgf Β1

Tumor progression is governed by various growth factors and cytokines in the tumor microenvironment (TME). Among these, transforming growth factor-β (TGF-β) is secreted by various cell types residing in the TME and promotes tumor progression by inducing the epithelial-to-mesenchymal transition (EMT) of cancer cells and tumor angiogenesis. TGF-β comprises three isoforms, TGF-β1, -β2, and -β3, and transduces intracellular signals via TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII). For the purpose of designing ligand traps that reduce oncogenic signaling in the TME, chimeric proteins comprising the ligand-interacting ectodomains of receptors fused with the Fc portion of immunoglobulin are often used. For example, chimeric soluble TβRII (TβRII-Fc) has been developed as an effective therapeutic strategy for targeting TGF-β ligands, but several lines of evidence indicate that TβRII-Fc more effectively traps TGF-β1 and TGF-β3 than TGF-β2, whose expression is elevated in multiple cancer types. In the present study, we developed a chimeric TGF-β receptor containing both TβRI and TβRII (TβRI-TβRII-Fc) and found that TβRI-TβRII-Fc trapped all TGF-β isoforms, leading to inhibition of both the TGF-β signal and TGF-β–induced EMT of oral cancer cells, whereas TβRII-Fc failed to trap TGF-β2. Furthermore, we found that TβRI-TβRII-Fc suppresses tumor growth and angiogenesis more effectively than TβRII-Fc in a subcutaneous xenograft model of oral cancer cells with high TGF-β expression. These results suggest that TβRI-TβRII-Fc may be a promising tool for targeting all TGF-β isoforms in the TME.

scholarly journals The Bisecting GlcNAc on N-Glycans Inhibits Growth Factor Signaling and Retards Mammary Tumor Progression

2010 ◽  
Vol 70 (8) ◽  
pp. 3361-3371 ◽  
Author(s):  
Yinghui Song ◽  
Jason A. Aglipay ◽  
Joshua D. Bernstein ◽  
Sumanta Goswami ◽  
Pamela Stanley
Keyword(s):  
Growth Factor ◽  
Tumor Progression ◽  
Mammary Tumor ◽  
Growth Factor Signaling ◽  
Mammary Tumor Progression ◽  
Bisecting Glcnac
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