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

Abstract

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 .

Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma

“…In addition, our further research showed that EPS1-1 regulated the expression of oncogenes and tumor suppressor genes, thereby through which might exert its biological function. These genes include cell proliferation promoting factors including CCND1 and c-Myc (Wang G. et al, 2019;Zhang D. et al, 2019), cell apoptosis regulators BAX and Bcl-2 (Zhang Q. et al, 2019;Hu et al, 2020), and factors that promote cell migration and invasion, such as Vimentin and Slug (Lillo Osuna et al, 2019;Shahid et al, 2019). Study by Song et al (2019) showed that EPS1-1 could reduce the expression of oncoproteins such as COX-2, β-catenin, CyclinD1, and C-Myc, and down-regulate the expression of proliferation-related proteins including Ki-67 and PCNA and the anti-apoptotic gene Bcl-2, up-regulate the expression of pro-apoptotic genes such as p53 and Bax, reduce the number of CD68, F4/80, and NF-κB positive cells, as well as reducing the concentrations of inflammatory factors in serum including TNF-α and IL-6.…”

Transcriptome profile of spleen tissues from locally-adapted Kenyan pigs (Sus scrofa) experimentally infected with three varying doses of a highly virulent African swine fever virus genotype IX isolate: Ken12/busia.1 (ken-1033)

“…The Hippo signaling pathway that controls animal organ size through cell proliferation and apoptosis regulation, including cell proliferation, apoptosis, and various stress responses [ 103 ], was significantly enriched in the medium and high dose groups (Supplementary Figs. 1 and 2 ).…”

Immunological significance of alternative splicing prognostic signatures for bladder cancer

“…Aerobic glycolysis inhibits the proliferation of hepatocellular carcinoma (HCC) cells by downregulating ACTG1, and a high level of ACTG1 is significantly related to advanced hepatoma [53]. HPCAL1 increases the proliferation and growth of glioblastoma by activating the Wnt/β-catenin pathway [54]. Yeon et al [55] found that 13.9% of colorectal cancers (CRCs) in 124 patients had ANK3 gene frameshift mutations and intratumoral heterogeneity, and low expression of ANK3 could inhibit detachment-induced apoptosis and promote CRC cell survival.…”