Mechanism of suppressors of cytokine signaling 1 inhibition of epithelial-mesenchymal transition signaling through ROS regulation in colon cancer cells: suppression of Src leading to thioredoxin up-regulation
| Autor: | Choong-Eun Lee, Sung Hoon Jung, Su-Min Kim |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition NF-E2-Related Factor 2 medicine.medical_treatment Active Transport Cell Nucleus Down-Regulation Vimentin Biology Transfection Antioxidants 03 medical and health sciences Suppressor of Cytokine Signaling 1 Protein Thioredoxins 0302 clinical medicine Downregulation and upregulation Cell Line Tumor medicine Humans Epithelial–mesenchymal transition reactive oxygen species chemistry.chemical_classification Reactive oxygen species Suppressor of cytokine signaling 1 thioredoxin Hydrogen Peroxide suppressors of cytokine signaling HCT116 Cells EMT signaling Up-Regulation Cell biology Gene Expression Regulation Neoplastic src-Family Kinases 030104 developmental biology Cytokine Oncology chemistry 030220 oncology & carcinogenesis Colonic Neoplasms embryonic structures biology.protein Snail Family Transcription Factors Thioredoxin Research Paper Src Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.11537 |
| Popis: | // Sung-Hoon Jung 1 , Su-Min Kim 1 , Choong-Eun Lee 1 1 Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 440-746, Korea Correspondence to: Choong-Eun Lee, email: celee@skku.edu Keywords: suppressors of cytokine signaling, reactive oxygen species, Src, thioredoxin, EMT signaling Received: February 26, 2016 Accepted: August 09, 2016 Published: August 23, 2016 ABSTRACT Reactive oxygen species (ROS) participate in malignant progression of cancers including epithelial-mesenchymal transition (EMT). We have investigated the role of suppressors of cytokine signaling (SOCS)1 as an inhibitor of ROS-induced EMT using colon cancer cell lines transduced with SOCS1 and shSOCS1. Hydrogen peroxide treatment induced EMT features such as elevation of vimentin and Snail with a corresponding reduction of E-cadherin. The EMT markers are significantly decreased upon SOCS1 over-expression while increased under SOCS1 knock-down. SOCS1 inhibited ROS signaling pathways associated with EMT such as Src, Jak, and p65. Of note, strong up-regulation of Src activity in SOCS1-ablated cells was responsible for the elevated signaling leading to EMT, as shSrc or Src inhibitor abolished the shSOCS1-induced promotion of EMT response. Suppression of ROS-inducible EMT markers and invasion in SOCS1 over-expressing cells correlated with significantly low intracellular ROS levels in these cells. Analysis of antioxidant enzymes in SOCS1-transduced cells revealed a selective up-regulation of thioredoxin (Trx1), while thioredoxin ablation restored ROS levels and the associated EMT markers. As a mechanism of thioredoxin up-regulation by SOCS1, inhibition of Src activity promoting nuclear translocation of Nrf-2 is proposed. Taken together, our data strongly indicate that SOCS1 antagonizes EMT by suppressing Src activity, leading to thioredoxin expression and down-regulation of ROS levels in colon cancer cells. |
| Databáze: | OpenAIRE |
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