title: Serum starvation regulates E-cadherin upregulation via activation of c-Src in non-small-cell lung cancer A549 cells.
abstract: E-cadherin is essential for the integrity of adherens junctions between lung epithelial cells, and the loss of E-cadherin allows cell motility and is thought to promote lung cancer metastasis. While the downregulation of E-cadherin expression has been well characterized and is seen with transforming growth factor-β1 (TGF-β1) exposure, few studies have focused on E-cadherin upregulation. Here, we show that serum starvation causes increased E-cadherin expression via the activation of c-Src kinase in non-small-cell lung cancer A549 cells. Serum starvation increased E-cadherin protein levels in a time- and dose-dependent manner. E-cadherin mRNA transcripts were unchanged with starvation, while protein translation inhibition with cycloheximide attenuated E-cadherin protein induction by starvation, suggesting that E-cadherin is regulated at the translational level by serum starvation. c-Src is a nonreceptor tyrosine kinase known to regulate protein translation machinery; serum starvation caused early and sustained activation of c-Src in A549 cells followed by E-cadherin upregulation. Furthermore, overexpression of a dominant negative c-Src attenuated the induction of E-cadherin by serum deprivation. Finally, we observed that TGF-β1 treatment attenuated the serum activation of c-Src as well as E-cadherin expression when cells were deprived of serum. In conclusion, our data demonstrate that the c-Src kinase is activated by serum starvation to increase E-cadherin expression in A549 cells, and these phenomena are antagonized by TGF-β1. These novel observations implicate the c-Src kinase as an upstream inducer of E-cadherin protein translation with serum starvation and TGF-β1 diametrically regulating c-Src kinase activity and thus E-cadherin abundance in A549 cells.
authors.affiliation: Department of Anesthesia, First Hospital of Jilin University, Changchun, Jilin, China; Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Su
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Khoo
authors.affiliation: Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Bowser
authors.affiliation: Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Weathington
authors.affiliation: Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Shuqi
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, First Hospital of Jilin University, Changchun, Jilin, China;
authors.forename: Haichun
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medicine and the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; and zhaoj@upmc.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
mesh_terms: D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015820:Cadherins; D016895:Culture Media, Serum-Free; D053773:Transforming Growth Factor beta1; D016392:Proto-Oncogene Proteins pp60(c-src)
keywords: E-cadherin; TGF-β1; c-Src; non-small-cell lung cancer; starvation