Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression

Background/Aims: Golgi phosphoprotein 3 (GOLPH3) plays pro-malignancy roles in several types of cancer. However, the molecular mechanism underlying GOLPH3 promoting tumor progression remains poorly understood. Methods: The expression of GOLPH3 and Wntless (Wls) in glioma tissues was examined by west...

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Main Authors: Dong Lu, Hao Zhang, Jiale Fu, Yanhua Qi, Xu Wang, Shishuang Wu, Xiuping Zhou, Rutong Yu
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-07-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/491618
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author Dong Lu
Hao Zhang
Jiale Fu
Yanhua Qi
Xu Wang
Shishuang Wu
Xiuping Zhou
Rutong Yu
author_facet Dong Lu
Hao Zhang
Jiale Fu
Yanhua Qi
Xu Wang
Shishuang Wu
Xiuping Zhou
Rutong Yu
author_sort Dong Lu
collection DOAJ
description Background/Aims: Golgi phosphoprotein 3 (GOLPH3) plays pro-malignancy roles in several types of cancer. However, the molecular mechanism underlying GOLPH3 promoting tumor progression remains poorly understood. Methods: The expression of GOLPH3 and Wntless (Wls) in glioma tissues was examined by western blotting and immunohistochemistry. EdU incorporation assay and colony formation assay was used to examine the cell growth ability. The effect of GOLPH3 on Wls recycling, Wnt secretion and β-catenin activity was detected using western blotting, immunofluorescence, RT-PCR, ELISA or luciferase assay. Results: The protein levels of GOLPH3 and Wls were upregulated and positively correlated with each other in human glioma tissues. The promoting effect of GOLPH3 on glioma cell proliferation was partially mediated by Wls. In addition, GOLPH3 interacted with Wls and GOLPH3 down-regulation drove Wls into lysosome for degradation, inhibiting its recycling to golgi and the plasma membrane. Importantly, GOLPH3 down-regulation inhibited Wnt2b secretion and decreased β-catenin level and transcription activity. Conclusions: This study provides a brand new evidence that GOLPH3 promotes glioma cell proliferation by facilitating Wls recycling and Wnt/β-catenin signaling. Our findings suggest a rationale for targeting the GOLPH3-Wls-Wnt axis as a promising therapeutic approach for glioblastoma.
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spelling doaj.art-59b658cba38b4252a32d4f419d019f712022-12-21T18:54:39ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-07-014762445245710.1159/000491618491618Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma ProgressionDong LuHao ZhangJiale FuYanhua QiXu WangShishuang WuXiuping ZhouRutong YuBackground/Aims: Golgi phosphoprotein 3 (GOLPH3) plays pro-malignancy roles in several types of cancer. However, the molecular mechanism underlying GOLPH3 promoting tumor progression remains poorly understood. Methods: The expression of GOLPH3 and Wntless (Wls) in glioma tissues was examined by western blotting and immunohistochemistry. EdU incorporation assay and colony formation assay was used to examine the cell growth ability. The effect of GOLPH3 on Wls recycling, Wnt secretion and β-catenin activity was detected using western blotting, immunofluorescence, RT-PCR, ELISA or luciferase assay. Results: The protein levels of GOLPH3 and Wls were upregulated and positively correlated with each other in human glioma tissues. The promoting effect of GOLPH3 on glioma cell proliferation was partially mediated by Wls. In addition, GOLPH3 interacted with Wls and GOLPH3 down-regulation drove Wls into lysosome for degradation, inhibiting its recycling to golgi and the plasma membrane. Importantly, GOLPH3 down-regulation inhibited Wnt2b secretion and decreased β-catenin level and transcription activity. Conclusions: This study provides a brand new evidence that GOLPH3 promotes glioma cell proliferation by facilitating Wls recycling and Wnt/β-catenin signaling. Our findings suggest a rationale for targeting the GOLPH3-Wls-Wnt axis as a promising therapeutic approach for glioblastoma.https://www.karger.com/Article/FullText/491618GliomaGOLPH3Wls RecyclingWnt secretionProliferation
spellingShingle Dong Lu
Hao Zhang
Jiale Fu
Yanhua Qi
Xu Wang
Shishuang Wu
Xiuping Zhou
Rutong Yu
Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression
Cellular Physiology and Biochemistry
Glioma
GOLPH3
Wls Recycling
Wnt secretion
Proliferation
title Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression
title_full Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression
title_fullStr Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression
title_full_unstemmed Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression
title_short Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression
title_sort golgi phosphoprotein 3 promotes wls recycling and wnt secretion in glioma progression
topic Glioma
GOLPH3
Wls Recycling
Wnt secretion
Proliferation
url https://www.karger.com/Article/FullText/491618
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