LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways.

LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways. Research Abstract Details 

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LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways. Abstract Text:

Minghua Wu,Qiong Chen,Dan Li,Xiaoling Li,Xiayu Li,Chen Huang,Yunlian Tang,Yanhong Zhou,Di Wang,Ke Tang,Li Cao,Shourong Shen,Guiyuan Li,Minghua Wu,Qiong Chen,Dan Li,Xiaoling Li,Xiayu Li,Chen Huang,Yunlian Tang,Yanhong Zhou,Di Wang,Ke Tang,Li Cao,Shourong Shen,Guiyuan Li,

Gliomas take a number of different genetic routes in the progression to glioblastoma multiforme, a highly invasive variant that is mostly unresponsive to current therapies. The alpha-chemokine stromal cell-derived factor (SDF)-1alpha binds to the seven transmembrane G-protein-coupled CXCR-4 receptor and acts to modulate cell migration and proliferation by activating multiple signal transduction pathways. Leucine-rich repeats containing 4 (LRRC4), a putative glioma suppressive gene, inhibits glioblastoma cells tumorigenesis in vivo and cell proliferation and invasion in vitro. We also previously demonstrated that LRRC4 controlled glioblastoma cells proliferation by ERK/AKT/NF-kappaB signaling pathway. In the present study, we demonstrate that CXC chemokine receptor 4 (CXCR4) is expressed in human glioblastoma U251 cell line, and that SDF-1alpha increases the proliferation, chemotaxis, and invasion in CXCR4(+) glioblastoma U251 cells through the activation of ERK1/2 and Akt. The reintroduction of LRRC4 in U251 cells inhibits the expression of CXCR4 and SDF-1alpha/CXCR4 axis-mediated downstream intracellular pathways such as ERK1/2 and Akt leading to proliferate, chemotactic and invasive effects. Furthermore, we provide evidence for proMMP-2 activation involvement in the SDF-1alpha/CXCR4 axis-mediated signaling pathway. LRRC4 significantly inhibits proMMP-2 activation by SDF-1alpha/CXCR4 axis-mediated ERK1/2 and Akt signaling pathway. Collectively, these results suggest a possible important "cross-talk" between LRRC4 and SDF-1alpha/CXCR4 axis-mediated intracellular pathways that can link signals of cell proliferation, chemotaxis and invasion in glioblastoma, and may represent a new target for development of new therapeutic strategies in glioma. J. Cell. Biochem. 103: 245-255, 2008. (c) 2007 Wiley-Liss, Inc.

LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways. Publishing Authors By Initials

M Wu,Q Chen,D Li,X Li,X Li,C Huang,Y Tang,Y Zhou,D Wang,K Tang,L Cao,S Shen,G Li,M Wu,Q Chen,D Li,X Li,X Li,C Huang,Y Tang,Y Zhou,D Wang,K Tang,L Cao,S Shen,G Li,

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LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of cellular biochemistry

VOLUME: 103

Page Numbers: 245-55

Journal Abbreviation: J. Cell. Biochem.

ISSN: 0730-2312

DAY: 1

MONTH: Jan

YEAR: 2008

LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways. Information

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LANGUAGE: eng

NlmUniqueID: 8205768

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AFFILIATION: Cancer Research Institute, Central South University, 110# Xiang-Ya Road, Changsha, 410078 Hunan, People's Republic of China.

Country: United States

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MEDLINETA: J Cell Biochem

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