title: Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells.
abstract: BACKGROUND
  Phospholipase C-γl (PLC-γl) is known to play a critical role in cell adhesion and migration and is highly expressed in metastatic tumors. In the current study, we found that cells transformed by PLC overexpression (PLC-γl cells) exhibited a marked decrease in expression of the Epo receptor (EpoR). Here, we assessed the role of EpoR-dependent signaling pathways in PLC-γl-dependent regulation of cell adhesion and migration.
  
  
  METHODS
  Expression and phosphorylation of EpoR and its functional role in PLC-γl cells were evaluated by immunoblot analysis or cell adhesion assay. The mechanism for PLC-γ1-induced EpoR downregulation was analyzed by blockage of proteosomal degradation with MG132. EpoR expression was also confirmed in colorectal cancer tissues in which PLC-γl was highly expressed.
  
  
  RESULTS
  EpoR was present on rat fibroblasts, where it functionally active and capable of increasing cell adhesion and migratory activity. However, PLC-γl cells significantly decreased the Epo-dependent effects via ubiquitination-proteosomal degradation of EpoR. A marked decrease of EpoR expression was confirmed in colorectal cancer tissues that showed high-level of PLC-γl expression.
  
  
  CONCLUSIONS
  The Epo/EpoR complex plays a critical role in the adhesion and migration of rat fibroblasts, and its functional inactivation is associated with PLC-γl-dependent reduction of cell-matrix adhesion and this also affects cell migration.
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pochen, Gyeonggido, South Korea.
authors.forename: Jin Ku
authors.initials: JK
authors.lastname: Kang
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Chang
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Nam
authors.forename: Sung-Kuk
authors.initials: SK
authors.lastname: Kim
authors.forename: Keun Jae
authors.initials: KJ
authors.lastname: Ahn
authors.forename: Heon
authors.initials: H
authors.lastname: Seok
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Yoon Joong
authors.initials: YJ
authors.lastname: Kang
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jo
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D016716:PC12 Cells; D051419:Paxillin / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051419:Paxillin; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D051966:Phospholipase C gamma; D046988:Proteasome Endopeptidase Complex