RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway

Yan,Yu; Jiang,Yugang

doi:10.3892/ijmm.2015.2421

RACK1 affects glioma cell growth and differentiation through the CNTN2-mediated RTK/Ras/MAPK pathway

Authors:
- Yu Yan
- Yugang Jiang
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Affiliations: Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
Published online on: November 30, 2015 https://doi.org/10.3892/ijmm.2015.2421
Pages: 251-257

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Abstract

Receptor for activated C kinase 1 (RACK1) and contactin-2 (CNTN2) are known to be abnormally expressed in gliomas; however, the association between RACK1 and CNTN2, and the effects of RACK1 and CNTN2 on glioma cell differentiation and the related molecular mechanisms remain largely unknown. The present study aimed to investigate the interaction between RACK1 and CNTN2, and to examine whether RACK1/CNTN2/receptor tyrosine kinase (RTK)/Ras/mitogen-activated protein kinase (MAPK) axis plays a role in glioma growth and differentiation. The results from western blot analysis revealed that the protein expression levels of RACK1 and CNTN2 were higher in high‑grade glioma tissues and cells, and lower in low-grade glioma tissues and cells. A co-immunoprecipitation assay demonstrated that RACK1 interacts with CNTN2, and RACK1 upregulated the expression of CNTN2. Gain-of‑function and loss-of‑function experiments indicated that both RACK1 and CNTN2 promoted glioma cell proliferation, inhibited glioma cell differentiation and activated the RTK/Ras/MAPK pathway. However, the effects of RACK1 on glioma cell proliferation, differentiation and the activation of the RTK/Ras/MAPK signaling pathway were abolished by the knockdown of CNTN2 using siRNA. In Therefore, the findings of this study firstly demonstrate that RACK1 interacts with CNTN2, and that the effects of RACK1 on glioma cell growth and differentiation are mediated by CNTN2. The RACK1/CNTN2/RTK/Ras/MAPK axis exists in glioma cells, and it may be a potential therapeutic target in gliomas.

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