title: P38/NF-κB/snail pathway is involved in caffeic acid-induced inhibition of cancer stem cells-like properties and migratory capacity in malignant human keratinocyte.
abstract: BACKGROUND
  Skin cancer is the most common cancer throughout the world. The epithelial-mesenchymal transition (EMT) and the acquisition of cancer stem cells (CSCs)-like properties emerge as critical steps in the metastasis of human skin cancers. Caffeic acid (CaA) exerts anticarcinogenic effects. However, the effects of CaA on the migratory capability and on the CSCs-like properties of skin cancer cells, and the molecular mechanisms underlying it are not fully understood.
  
  
  METHODS
  Malignant HaCaT cells were treated by CaA. Transwell assay was performed to determine that CaA attenuated the migratory capability; Spheroid formation assay was performed to confirm that CaA decreased the CSCs-like phenotype; Treated malignant HaCaT cells were molecularly characterized by RT-PCR, Western blots, Southwestern blot, and immunoprecipitation.
  
  
  RESULTS
  In CaA-treated malignant human keratinocyte (malignant HaCaT cells), inhibition of the migratory capability and CSCs-like phenotype were observed. CaA up-regulated the phosphorylation of p38, and down-regulated the activation of nuclear factor κB (NF-κB)/snail signal pathway. Indeed, p38 decreased the DNA-binding activity of NF-κB to the promoter of snail gene, which resulted in the transcriptional inactivation of snail. Blockage of p38 attenuated the CaA-induced inhibition of migratory capability and CSCs-like phenotype in malignant HaCaT cells.
  
  
  CONCLUSIONS
  CaA attenuates the migratory capability and CSCs-like Properties of malignant human keratinocyte, in which, p38-mediated down-regulation of NF-κB/snail signal pathway is involved.
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Kebo
authors.initials: K
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenqin
authors.initials: W
authors.lastname: Yin
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D054338:Cell Transdifferentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D002109:Caffeic Acids; D016328:NF-kappa B; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; C040048:caffeic acid