Antitumor effect of memantine is related to the formation of the splicing isoform of GLG1, a decoy FGF‑binding protein

Yamaguchi,Fumio; Hayakawa,Sumio; Kawashima,Shota; Asakura,Takayuki; Oishi,Yumiko

doi:10.3892/ijo.2022.5370

Antitumor effect of memantine is related to the formation of the splicing isoform of GLG1, a decoy FGF‑binding protein

Authors:
- Fumio Yamaguchi
- Sumio Hayakawa
- Shota Kawashima
- Takayuki Asakura
- Yumiko Oishi
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Affiliations: Department of Neurosurgery for Community Health, Nippon Medical School, Tokyo 1138603, Japan, Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo 1138603, Japan, Faculty of Medicine, Nippon Medical School, Tokyo 1138603, Japan
Published online on: May 11, 2022 https://doi.org/10.3892/ijo.2022.5370
Article Number: 80

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Abstract

Drug repositioning is a strategy for repurposing the approved or investigational drugs that are outside the scope of the original medical indication. Memantine is used as a non‑competitive N‑methyl‑D‑aspartate receptor antagonist to prevent glutamate‑mediated excitotoxicity in Alzheimer's disease, and is one of the promising agents which is utilized for the purpose of cancer therapy. However, the association between memantine and Golgi glycoprotein 1 (GLG1), an intracellular fibroblast growth factor receptor, in cancers has not yet been clarified. The present study analyzed the expression and location of GLG1 in tumor cells treated with memantine. Memantine was found to suppress the growth of malignant glioma and breast cancer cells in a concentration‑dependent manner. The mRNA expression of GLG1 was upregulated in a concentration‑dependent manner, and the splicing variant profiles were altered in all cell lines examined. The results of western blot analysis revealed an increase in the full‑length and truncated forms of GLG1. Moreover, GLG1 spread in the cytosol of memantine‑treated cells, whereas it localized in the Golgi apparatus in control cells. Since GLG1 functions as a decoy FGF receptor, the modulation of GLG1 may prove to be one of the mechanisms underlying the cancer‑suppressive effects of memantine.

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