Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells

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

doi:10.1007/s13402-010-0001-9

Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells

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

Department of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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-γl 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 ubiquitinationproteosomal 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-γldependent reduction of cell-matrix adhesion and this also affects cell migration.

Original language	English
Pages (from-to)	11-21
Number of pages	11
Journal	Cellular oncology (Dordrecht)
Volume	34
Issue number	1
DOIs	https://doi.org/10.1007/s13402-010-0001-9
State	Published - Feb 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cell adhesion and migration/metastasis
Colorectal cancer
Erythropoietin (Epo)
Erythropoietin Receptor (EpoR)
Focal contact formation
Paxillin
Phospholipase C-gamma 1 (PLC-γ1)
Proteosomal protein degradation

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10.1007/s13402-010-0001-9

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Kang, J. K., Chang, C. H., Nam, H. J., Kim, S. K., Ahn, K. J., Seok, H., Park, S. J., Kang, Y. J., Jo, Y. S., Shong, M., & Kim, H. (2011). Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells. Cellular oncology (Dordrecht), 34(1), 11-21. https://doi.org/10.1007/s13402-010-0001-9

@article{42e143fbae284c478afc096bb65c828d,

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-γl 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 ubiquitinationproteosomal 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-γldependent reduction of cell-matrix adhesion and this also affects cell migration.",

keywords = "Cell adhesion and migration/metastasis, Colorectal cancer, Erythropoietin (Epo), Erythropoietin Receptor (EpoR), Focal contact formation, Paxillin, Phospholipase C-gamma 1 (PLC-γ1), Proteosomal protein degradation",

author = "Kang, \{Jin Ku\} and Chang, \{Chang Hyun\} and Nam, \{Hyo Jung\} and Kim, \{Sung Kuk\} and Ahn, \{Keun Jae\} and Heon Seok and Park, \{Sang Joon\} and Kang, \{Yoon Joong\} and Jo, \{Young Suk\} and Minho Shong and Ho Kim",

year = "2011",

month = feb,

doi = "10.1007/s13402-010-0001-9",

language = "English",

volume = "34",

pages = "11--21",

journal = "Cellular oncology (Dordrecht)",

issn = "2211-3428",

publisher = "Springer Science and Business Media B.V.",

number = "1",

}

TY - JOUR

T1 - Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells

AU - Kang, Jin Ku

AU - Chang, Chang Hyun

AU - Nam, Hyo Jung

AU - Kim, Sung Kuk

AU - Ahn, Keun Jae

AU - Seok, Heon

AU - Park, Sang Joon

AU - Kang, Yoon Joong

AU - Jo, Young Suk

AU - Shong, Minho

AU - Kim, Ho

PY - 2011/2

Y1 - 2011/2

N2 - 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-γl 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 ubiquitinationproteosomal 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-γldependent reduction of cell-matrix adhesion and this also affects cell migration.

AB - 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-γl 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 ubiquitinationproteosomal 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-γldependent reduction of cell-matrix adhesion and this also affects cell migration.

KW - Cell adhesion and migration/metastasis

KW - Colorectal cancer

KW - Erythropoietin (Epo)

KW - Erythropoietin Receptor (EpoR)

KW - Focal contact formation

KW - Paxillin

KW - Phospholipase C-gamma 1 (PLC-γ1)

KW - Proteosomal protein degradation

UR - https://www.scopus.com/pages/publications/80052527859

U2 - 10.1007/s13402-010-0001-9

DO - 10.1007/s13402-010-0001-9

M3 - Article

C2 - 21360263

AN - SCOPUS:80052527859

SN - 2211-3428

VL - 34

SP - 11

EP - 21

JO - Cellular oncology (Dordrecht)

JF - Cellular oncology (Dordrecht)

IS - 1

ER -

Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells

Abstract

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Keywords

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