title: P130cas is required for TGF-β1-mediated epithelial-mesenchymal transition in lung cancer.
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.
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors: Bo
authors: B
authors: Deng
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors: Qun-You
authors: QY
authors: Tan
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors: Ru-Wen
authors: RW
authors: Wang
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors: Yao-Guang
authors: YG
authors: Jiang
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors: Jing-Hai
authors: JH
authors: Zhou
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.
authors: Wei
authors: W
authors: Huang
keywords: P130cas; TGF-β1; breast cancer anti-estrogen resistance protein 1; epithelial-mesenchymal transition; non-small cell lung cancer; p38