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Effects of cerulein on keratin 8 phosphorylation and perinuclear reorganization in pancreatic cancer cells: Involvement of downregulation of protein phosphatase 2A and alpha4
Author(s) -
Park Mi Kyung,
Lee Chang Hoon
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22186
Subject(s) - phosphorylation , protein phosphatase 2 , phosphatase , mapk/erk pathway , kinase , microbiology and biotechnology , downregulation and upregulation , chemistry , cancer research , biology , biochemistry , gene
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.