Abstract
In lung cancer A549 cells, the present study evaluated the associations between p130cas expression and the activation of p38 or Smad2, which are components of two of the main signaling pathways of transforming growth factor-β1 (TGF-β1), i.e., epithelial-mesenchymal transition (EMT) and apoptosis, respectively. TGF-β1-induced EMT was investigated by inspecting cell shape and cell migration, and by testing E-Cadherin, N-Cadherin and Vimentin biomarkers in p130cas-RNA interference (RNAi)-A549 cells. The changes in TGF-β1-induced apoptosis, i.e., cleaved Caspase-3 levels, were additionally analyzed following p130cas-RNAi. p130cas-knockdown decreased the phosphorylated (p)-p38 expression level, and blockaded the TGF-β1-induced activation of p-p38 in the A549 cells. p130cas-knockdown arrested cell migration and impaired TGF-β1-induced EMT in the A549 cells, characterized by changes in cell morphology and biomarker levels. However, p130cas-knockdown had no impact on the activation of Smad2 and the cleavage of Caspase-3. These results indicate that p130cas is a novel molecular ‘rheostat’ that alters the function of the TGF-β1 signaling pathway from tumor suppression to tumor promotion in lung cancer cells. The underlying mechanism warrants further study.
Highlights
In lung cancer A549 cells, the present study evaluated the associations between p130cas expression and the activation of p38 or Smad2, which are components of two of the main signaling pathways of transforming growth factor‐β1 (TGF‐β1), i.e., epithelial-mesenchymal transition (EMT) and apoptosis, respectively
Elevating the expression of either the full‐length or just the carboxyl terminus of p130Cas in mammary epithelial cells has been shown to diminish the ability of transforming growth factor‐β1 (TGF‐β1) to activate Smad2/3, but increase its coupling to p38 mitogen-activated protein kinases (MAPKs; p38) [4,5], whose activation is required for TGF‐β1 mediated fibroblastic transdifferentiation and cell migration [6]
TGF‐β1 has been found to be upregulated in a variety of tumors [17,18,19], and plays significant roles in EMT and metastasis [12]
Summary
In lung cancer A549 cells, the present study evaluated the associations between p130cas expression and the activation of p38 or Smad, which are components of two of the main signaling pathways of transforming growth factor‐β1 (TGF‐β1), i.e., epithelial-mesenchymal transition (EMT) and apoptosis, respectively. P130cas‐knockdown had no impact on the activation of Smad and the cleavage of Caspase‐3 These results indicate that p130cas is a novel molecular ‘rheostat’ that alters the function of the TGF‐β1 signaling pathway from tumor suppression to tumor promotion in lung cancer cells. Our previous study demonstrated that p130cas‐knockdown reduced the phosphorylated‐p38 (p‐p38) level in lung cancer A549 cells [4], indicating the significance of p130cas in p38 activation and the subsequent occurrence of EMT. The aim was to clarify the significant alteration of the TGF‐β1 signaling pathways from tumor suppression to tumor promotion by the regulation of p130cas
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