Open AccessHPCAL 1 promotes glioblastoma proliferation via activation of Wnt/β‐catenin signalling pathway
Author(s) -
Zhang Dongming,
Liu Xidong,
Xu Xuebin,
Xu Jianmeng,
Yi Zhongjun,
Shan Baochang,
Liu Bing
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14083
Subject(s) - gene knockdown , wnt signaling pathway , cell growth , gene silencing , cancer research , microbiology and biotechnology , ectopic expression , biology , mapk/erk pathway , phosphorylation , transcription factor , signal transduction , chemistry , cell culture , gene , biochemistry , genetics
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 ( HPCAL 1) serves as a sensor of Ca 2+ . However, the understanding of HPCAL 1 activity in GBM is limited. The present study revealed that the gene HPCAL 1 was up‐regulated by Ca 2+ in the tissues and cells of GBM . Ectopic expression of HPCAL 1 promoted proliferation of cells. Exhaustion of HPCAL 1 inhibited cell growth not only in vivo, but also in vitro. In addition, HPCAL 1 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 GSK 3β was significantly decreased after HPCAL 1 knockdown in GBM cells, and knockdown of the gene GSK 3 β in GBM cells enhanced cell proliferation and promoted transcription of the genes CCND 1 and c‐Myc . Furthermore, the phosphorylation of ERK was decreased in the cells with HPCAL 1 knockdown, while it was promoted via overexpression of HPCAL 1 . The suppression or depletion of the gene ERK decreased proliferation triggered by overexpression of HPCAL 1 and impaired transcription of the genes c‐Myc and CCND 1. These studies elucidate the tumour‐promoting activity of HPCAL 1. They also offer an innovative therapeutic strategy focusing on the HPCAL 1‐Wnt/β‐catenin axis to regulate proliferation and development of GBM .