title: Effects of cerulein on keratin 8 phosphorylation and perinuclear reorganization in pancreatic cancer cells: Involvement of downregulation of protein phosphatase 2A and alpha4.
abstract: Toxicants can perturb cellular homeostasis by modifying phosphorylation-based signaling. In the present study, we examined the effects of cerulein, an inducer of acute pancreatitis, on keratin 8 (K8) phosphorylation. We found that cerulein dose-dependently induced K8 phosphorylation and perinuclear reorganization in PANC-1 cells, thus leading to migration and invasion. The extracellular signal-regulated kinases (ERK) inhibitor U0126 suppressed cerulein-induced phosphorylation of serine 431 and reorganization of K8. Cerulein reduced the expressions of protein phosphatase 2A (PP2A) via ubiqutination and alpha4. PP2A's involvement in K8 phosphorylation of PANC-1 cells was also confirmed by the observation that PP2A gene silencing resulted in K8 phosphorylation and migration of PANC-1 cells. Overall, these results suggest that cerulein induced phosphorylation and reorganization through ERK activation by downregulating PP2A and alpha4, leading to increased migration and invasion of PANC-1 cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2090-2098, 2016.
authors: BK21PLUS R-FIND Team, College of Pharmacy, Dongguk University, Seoul, 100-715, Republic of Korea.
authors: Mi Kyung
authors: MK
authors: Park
authors: BK21PLUS R-FIND Team, College of Pharmacy, Dongguk University, Seoul, 100-715, Republic of Korea.
authors: Chang Hoon
authors: CH
authors: Lee
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002108:Ceruletide / Q000633:toxicity*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D053533:Keratin-8 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010190:Pancreatic Neoplasms; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002070:Butadienes; D053533:Keratin-8; D009570:Nitriles; C113580:U 0126; D012694:Serine; D002108:Ceruletide; D048049:Extracellular Signal-Regulated MAP Kinases; D054648:Protein Phosphatase 2
keywords: alpha4; cerulean; keratin 8 phosphorylation; keratin 8 reorganization; protein phosphatase 2A