title: Interleukin-17A inhibits cell autophagy under starvation and promotes cell migration via TAB2/TAB3-p38 mitogen-activated protein kinase pathways in hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is characterized by progressive development and poor prognosis against a background of chronic inflammation. Interleukin (IL)-17A is an important proinflammatory cytokine that contributes to inflammatory pathology and tumor microenvironment. Research on autophagy has increasingly focused on its role in inflammation. Thus, we investigated the effect of IL-17A on the progression of HCC through the autophagic pathway.
  
  
  METHODS
  The expression and prognostic values of IL-17A and autophagic gene Beclin-1 were determined using immunohistochemistry in 83 HCC patients after resection. The effects and underlying molecular mechanisms of IL-17A on human HCC were explored in vitro using recombinant human IL-17A.
  
  
  RESULTS
  High expression of IL-17A and low expression of Beclin-1 were associated with worse TNM stage in HCC patients. And the level of autophagy was lower in tumor tissues compared with tumor-adjacent tissues. In vitro, recombinant human IL-17A inhibited starvation-induced autophagy and maintained cell viability through activating TAK1-binding protein 2 (TAB2 and TAK1-binding protein 3 (TAB3)-inducing p38 mitogen-activated protein kinase (MAPK) in Huh7 and HepG2 HCC cells. IL-17A promoted migration of HCC cells through the TAB2/p38 MAPK and TAB3/p38 MAPK pathways.
  
  
  CONCLUSIONS
  IL-17A promotes migration of HCC cells and prevents autophagic cell death from starvation by activating TAB2/p38 MAPK and TAB3/p38 MAPK.
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. njsxl2000@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: P-W
authors.initials: PW
authors.lastname: Wu
authors.forename: X-W
authors.initials: XW
authors.lastname: Yuan
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: X-L
authors.initials: XL
authors.lastname: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C508717:IL17A protein, human; D020381:Interleukin-17; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C410585:TAB2 protein, human; C481053:TAB3 protein, human; D048051:p38 Mitogen-Activated Protein Kinases