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HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway

Glioblastoma (GBM) is the most prevalent primary malignancy of the central nervous system with obvious aggressiveness, and is associated with poor clinical outcome. Studies have indicated that calcium ion (Ca(2+)) can positively regulate the initiation of malignancy with regard to GBM by modulating...

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Autores principales: Zhang, Dongming, Liu, Xidong, Xu, Xuebin, Xu, Jianmeng, Yi, Zhongjun, Shan, Baochang, Liu, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484330/
https://www.ncbi.nlm.nih.gov/pubmed/30843345
http://dx.doi.org/10.1111/jcmm.14083
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author Zhang, Dongming
Liu, Xidong
Xu, Xuebin
Xu, Jianmeng
Yi, Zhongjun
Shan, Baochang
Liu, Bing
author_facet Zhang, Dongming
Liu, Xidong
Xu, Xuebin
Xu, Jianmeng
Yi, Zhongjun
Shan, Baochang
Liu, Bing
author_sort Zhang, Dongming
collection PubMed
description Glioblastoma (GBM) is the most prevalent primary malignancy of the central nervous system with obvious aggressiveness, and is associated with poor clinical outcome. Studies have indicated that calcium ion (Ca(2+)) can positively regulate the initiation of malignancy with regard to GBM by modulating quiescence, proliferation, migration and maintenance. Hippocalcin like‐1 protein (HPCAL1) serves as a sensor of Ca(2+). However, the understanding of HPCAL1 activity in GBM is limited. The present study revealed that the gene HPCAL1 was up‐regulated by Ca(2+) in the tissues and cells of GBM. Ectopic expression of HPCAL1 promoted proliferation of cells. Exhaustion of HPCAL1 inhibited cell growth not only in vivo, but also in vitro. In addition, HPCAL1 enhanced the Wnt pathway by stimulating β‐catenin accumulation and nuclear translocation in GBM cells, while β‐catenin silencing significantly inhibited the proliferation and growth of the GBM cells. Our results showed that Ser9 phosphorylation of GSK3β was significantly decreased after HPCAL1 knockdown in GBM cells, and knockdown of the gene GSK3β in GBM cells enhanced cell proliferation and promoted transcription of the genes CCND1 and c‐Myc. Furthermore, the phosphorylation of ERK was decreased in the cells with HPCAL1 knockdown, while it was promoted via overexpression of HPCAL1. The suppression or depletion of the gene ERK decreased proliferation triggered by overexpression of HPCAL1 and impaired transcription of the genes c‐Myc and CCND1. These studies elucidate the tumour‐promoting activity of HPCAL1. They also offer an innovative therapeutic strategy focusing on the HPCAL1‐Wnt/β‐catenin axis to regulate proliferation and development of GBM.
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spelling pubmed-64843302019-05-03 HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway Zhang, Dongming Liu, Xidong Xu, Xuebin Xu, Jianmeng Yi, Zhongjun Shan, Baochang Liu, Bing J Cell Mol Med Original Articles Glioblastoma (GBM) is the most prevalent primary malignancy of the central nervous system with obvious aggressiveness, and is associated with poor clinical outcome. Studies have indicated that calcium ion (Ca(2+)) can positively regulate the initiation of malignancy with regard to GBM by modulating quiescence, proliferation, migration and maintenance. Hippocalcin like‐1 protein (HPCAL1) serves as a sensor of Ca(2+). However, the understanding of HPCAL1 activity in GBM is limited. The present study revealed that the gene HPCAL1 was up‐regulated by Ca(2+) in the tissues and cells of GBM. Ectopic expression of HPCAL1 promoted proliferation of cells. Exhaustion of HPCAL1 inhibited cell growth not only in vivo, but also in vitro. In addition, HPCAL1 enhanced the Wnt pathway by stimulating β‐catenin accumulation and nuclear translocation in GBM cells, while β‐catenin silencing significantly inhibited the proliferation and growth of the GBM cells. Our results showed that Ser9 phosphorylation of GSK3β was significantly decreased after HPCAL1 knockdown in GBM cells, and knockdown of the gene GSK3β in GBM cells enhanced cell proliferation and promoted transcription of the genes CCND1 and c‐Myc. Furthermore, the phosphorylation of ERK was decreased in the cells with HPCAL1 knockdown, while it was promoted via overexpression of HPCAL1. The suppression or depletion of the gene ERK decreased proliferation triggered by overexpression of HPCAL1 and impaired transcription of the genes c‐Myc and CCND1. These studies elucidate the tumour‐promoting activity of HPCAL1. They also offer an innovative therapeutic strategy focusing on the HPCAL1‐Wnt/β‐catenin axis to regulate proliferation and development of GBM. John Wiley and Sons Inc. 2019-03-06 2019-05 /pmc/articles/PMC6484330/ /pubmed/30843345 http://dx.doi.org/10.1111/jcmm.14083 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zhang, Dongming
Liu, Xidong
Xu, Xuebin
Xu, Jianmeng
Yi, Zhongjun
Shan, Baochang
Liu, Bing
HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway
title HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway
title_full HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway
title_fullStr HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway
title_full_unstemmed HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway
title_short HPCAL1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway
title_sort hpcal1 promotes glioblastoma proliferation via activation of wnt/β‐catenin signalling pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484330/
https://www.ncbi.nlm.nih.gov/pubmed/30843345
http://dx.doi.org/10.1111/jcmm.14083
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