title: Dexamethasone Inhibits TGF-β1-Induced Cell Migration by Regulating the ERK and AKT Pathways in Human Colon Cancer Cells Via CYR61.
abstract: OBJECTIVE
  One of the features in cancer development is the migration of cancer cells to form metastatic lesions. CYR61 protein promotes migration and the epithelial-mesenchymal transition in several cancer cell types. Evidence suggests that CYR61 and dexamethasone are relevant to colorectal cancer. However, relationships between them and colorectal cancer are still unclear. Understanding the molecular mechanism of colorectal cancer progression related with CYR61 and dexamethasone, which is widely used for combination chemotherapy, is necessary for improved therapy.
  
  
  METHODS
  We used colorectal cancer cells, HCT116, co-treated with transforming growth factor β1 (TGF-β1) and dexamethasone to examine the inhibitory migration effect of dexamethasone by migratory assay. Alternatively, both migratory pathways, expression of AKT and ERK, and the target factor CYR61 was also tested by co-treatment with TGF-β1 and dexamethasone.
  
  
  RESULTS
  We report that dexamethasone significantly inhibited TGF-β1-induced cell migration, without affecting cell proliferation. Importantly, we observed that TGF-β1 promoted the epithelial-mesenchymal transition process and that dexamethasone co-treatment abolished this effect. ERK and AKT signaling pathways were found to mediate TGF-β1-induced migration, which was inhibited by dexamethasone. In addition, TGF-β1 treatment induced CYR61 expression whereas dexamethasone reduced it. These observations were compatible with the modulation of migration observed following treatment of HCT116 cells with human recombinant CYR61 and anti-CYR61 antibody. Our results also indicated that TGF-β1 enhanced collagen I and reduced matrix metalloproteinase 1 expression, which was reversed by dexamethasone treatment.
  
  
  CONCLUSIONS
  These findings suggested that dexamethasone inhibits AKT and ERK phosphorylation, leading to decreased CYR61 expression, which in turn blocks TGF-β1-induced migration.
authors.affiliation: Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Biochemistry, Jeju National University School of Medicine, Jeju, Korea.
authors.forename: Ngoc Thuy
authors.initials: NT
authors.lastname: Bui
authors.affiliation: Department of Biochemistry, Jeju National University School of Medicine, Jeju, Korea.
authors.forename: Manh Tin
authors.initials: MT
authors.lastname: Ho
authors.affiliation: Department of Biochemistry, Jeju National University School of Medicine, Jeju, Korea.
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Jeju National University School of Medicine, Jeju, Korea.
authors.forename: Moonjae
authors.initials: M
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Dong Bok
authors.initials: DB
authors.lastname: Shin
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015820:Cadherins; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology*; D055515:Cysteine-Rich Protein 61 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D018450:Disease Progression; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D018931:Antineoplastic Agents, Hormonal; D015820:Cadherins; D024042:Collagen Type I; D055515:Cysteine-Rich Protein 61; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D003907:Dexamethasone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Colon; Cysteine-rich protein 61; Dexamethasone