Downregulation of Erythropoietin Receptor by Overexpression of Phospholipase C-gamma 1 is Critical for Decrease on Focal Adhesion in Transformed Cells

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2011 Mar 2

PMID 21360263

Citations 5

Authors

Jin Ku Kang

Chang-Hyun Chang

Hyo Jung Nam

Sung-Kuk Kim

Keun Jae Ahn

Heon Seok

Sang Joon Park

Yoon Joong Kang

Young Suk Jo

Minho Shong

Ho Kim

Affiliations

Soon will be listed here.

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.

Citing Articles

Enhancement of Farnesoid X Receptor Inhibits Migration, Adhesion and Angiogenesis through Proteasome Degradation and VEGF Reduction in Bladder Cancers.

Lai C, Wang H, Chang H, Tsai Y, Tsai W, Lee C Int J Mol Sci. 2022; 23(9).

PMID: 35563650 PMC: 9103877. DOI: 10.3390/ijms23095259.

Phospholipase Cγ1 links inflammation and tumorigenesis in colitis-associated cancer.

Park K, Kim K, Oh T, Kang D, Kim E, Yang Y Oncotarget. 2018; 9(5):5752-5763.

PMID: 29464031 PMC: 5814171. DOI: 10.18632/oncotarget.23430.

Progress in detecting cell-surface protein receptors: the erythropoietin receptor example.

Elliott S, Sinclair A, Collins H, Rice L, Jelkmann W Ann Hematol. 2013; 93(2):181-92.

PMID: 24337485 PMC: 3890056. DOI: 10.1007/s00277-013-1947-2.

Epo receptors are not detectable in primary human tumor tissue samples.

Elliott S, Swift S, Busse L, Scully S, Van G, Rossi J PLoS One. 2013; 8(7):e68083.

PMID: 23861852 PMC: 3701640. DOI: 10.1371/journal.pone.0068083.

The effect of erythropoietin on normal and neoplastic cells.

Elliott S, Sinclair A Biologics. 2012; 6:163-89.

PMID: 22848149 PMC: 3402043. DOI: 10.2147/BTT.S32281.

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