title: A study of death by anoikis in cultured epithelial cells.
abstract: BACKGROUND
  Epithelial cells are critically dependent upon cell-matrix and cell-cell adhesion for growth and survival. Anoikis is programmed cell death caused by disruption of cell-substrate adhesion in normal epithelial cells.
  
  
  METHODS
  We studied the induction of anoikis in vitro in two cell lines; HaCaT and SW742. PI3K, JAK2 and PKC are key elements in signalling pathways regulating cell survival, and using specific inhibitors we also examined their potential role in the induction of anoikis.
  
  
  RESULTS
  When prevented from adhesion by culture on polyHEMA, HaCaT cells underwent apoptosis selectively from the proliferating population; surviving cells underwent cell cycle arrest. In SW742 cells anoikis also occurred, but was balanced by increased cycling. The effects of specific kinase inhibitors indicated that both Janus kinase 2 and protein kinase C partially protect HaCaT cells from anoikis through inducing cell cycle arrest of surviving nonadherent cells; inhibition of Phosphatidylinositol 3-kinase did not induce cycling in HaCaTs prevented from adhesion but did stimulate anoikis. SW742 cells showed markedly different responses: Janus kinase 2 inhibition activated apoptosis directly, Phosphatidylinositol 3-kinase inhibition stimulated both cell cycling and apoptosis, while protein kinase C inhibition stimulated cycling but inhibited apoptosis.
  
  
  CONCLUSIONS
  Susceptibility to cell death in adhesion-prevented epithelial cells may thus be regulated by signalling pathways involving Phosphatidylinositol 3-kinase, Janus kinase 2 and protein kinase C. The ability of epithelial tumour cells to invade and metastasize may therefore result from disruption of these pathways.
authors.affiliation: Royal Holloway, University of London, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bretland
authors.forename: J
authors.initials: J
authors.lastname: Lawry
authors.forename: R M
authors.initials: RM
authors.lastname: Sharrard
mesh_terms: D023102:Anoikis / Q000502:physiology*; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011102:Polyhydroxyethyl Methacrylate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D001973:Bromodeoxyuridine; D004791:Enzyme Inhibitors; D053614:Janus Kinase 2; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011102:Polyhydroxyethyl Methacrylate; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; C507924:JAK2 protein, human