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- Title
Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells.
- Authors
Kang, Jin; Chang, Chang-Hyun; Nam, Hyo; Kim, Sung-Kuk; Ahn, Keun; Seok, Heon; Park, Sang; Kang, Yoon; Jo, Young; Shong, Minho; Kim, Ho
- 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. Conclusion: 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.
- Subjects
ERYTHROPOIETIN receptors; PHOSPHOLIPASE C; CELL adhesion; COLON cancer; IMMUNOBLOTTING; PHOSPHORYLATION; CELL-matrix adhesions
- Publication
Cellular Oncology (2211-3428), 2011, Vol 34, Issue 1, p11
- ISSN
2211-3428
- Publication type
Article
- DOI
10.1007/s13402-010-0001-9