Abstract
Transforming growth factor-β (TGF-β) responsiveness in cultured cells can be modulated by TGF-β partitioning between lipid raft/caveolae- and clathrin-mediated endocytosis pathways. Lipid rafts are plasma membrane microdomains with an important role in cell survival signaling, and cholesterol is necessary for the lipid rafts’ structure and function. Euphol is a euphane-type triterpene alcohol that is structurally similar to cholesterol and has a wide range of pharmacological properties, including anti-inflammatory and anti-cancer effects. In the present study, euphol suppressed TGF-β signaling by inducing TGF-β receptor movement into lipid-raft microdomains and degrading TGF-β receptors.
Highlights
Transforming growth factor-β is a family of 25-kDa disulfide-linked dimeric proteins
We previously reported that a high concentration of cholesterol in the culture medium suppresses Transforming growth factor-β (TGF-β) responsiveness in cultured cells by causing accumulation of cell-surface TGF-βTGF-β receptor complexes in lipid rafts/caveolae of the plasma membrane, facilitating rapid degradation of these complexes, and attenuating TGF-β-stimulated signaling and related responses [22,23,24]
The polyclonal antibodies against early endosome antigen 1 (EEA1), transferrin receptor (TfR), Smad2, fibronectin, lamin B, EGF receptor, flotillin1, flotillin-2, CD-55, caveolin-1, TβR-I, and TβR-II were obtained from Santa Cruz (Santa Cruz, CA)
Summary
Transforming growth factor-β is a family of 25-kDa disulfide-linked dimeric proteins. TGF-β exhibits bifunctional growth regulation: it inhibits the growth of most cell types, including epithelial cells, endothelial cells and lymphocytes; and it stimulates proliferation of mesenchymal cells such as fibroblasts [1, 2]. TGFβ inhibits cell proliferation, induces apoptosis, and mediates differentiation, suggesting that TGF-β signaling has a tumor suppressing effect in epithelial tumors [3, 4]. TGF-β promotes invasion and metastasis in late stage tumors, indicating its effect on human cancers depends on the stage of the cancer. In addition to growth regulation, TGF-β regulates the synthesis of the extracellular matrix, chemotaxis, angiogenesis, and differentiation of several cell lineages. TGF-β signaling has been implicated in many pathophysiological processes, including
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