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

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

UN SDGs

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

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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 - http://www.scopus.com/inward/record.url?scp=80052527859&partnerID=8YFLogxK

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

Keywords

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