title: Depletion of GRIM-19 accelerates hepatocellular carcinoma invasion via inducing EMT and loss of contact inhibition.
abstract: Genes associated with retinoid-interferon-induced mortality 19 (GRIM-19) was identified as a tumor suppressor protein associated with apoptosis and growth inhibition. Here, we report that the expression levels of GRIM-19 are significantly attenuated in hepatocellular carcinoma (HCC) patients with deteriorating differentiation states, hepatic capsule invasion and microvascular invasion, suggesting the potential role of GRIM-19 not only at the origin but also in the invasive progression of HCCs. To dissect the possible mechanisms by which GRIM-19 regulates tumor cell invasion, we established the hepatic HL-7702 and HCC Huh-7 cell lines stably depleted of GRIM-19. Results show that downregulation of GRIM-19 induces a morphological transformation resembling epithelial-mesenchymal transition (EMT) as well as aberrant expression of epithelial and mesenchymal molecular markers. Additionally, these cells lose contact inhibition, a phenomenon of cessation of cell migration in contact with neighboring cells, as assessed by cell imaging, growth curve and S-phase transition in confluent conditions.
  
  
  CONCLUSIONS
  Our observations demonstrate a novel mechanistic insight into a critical role of GRIM-19 in HCC invasive potential.
authors: Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, PR China.
authors: Hongbo
authors: H
authors: Hao
authors: Jun
authors: J
authors: Liu
authors: Guoliang
authors: G
authors: Liu
authors: Dongshi
authors: D
authors: Guan
authors: Yang
authors: Y
authors: Yang
authors: Xiuqing
authors: X
authors: Zhang
authors: Xinmin
authors: X
authors: Cao
authors: Qian
authors: Q
authors: Liu
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D003260:Contact Inhibition / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human