Neurodegeneration-associated protein VAPB regulates proliferation in medulloblastoma

神经退行性相关蛋白 VAPB 调节髓母细胞瘤的增殖

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作者:Amanda Faria Assoni, Thiago Giove Mitsugi, René Wardenaar, Raiane Oliveira Ferreira, Elisa Helena Farias Jandrey, Gabriela Machado Novaes, Isabela Fonseca de Oliveira Granha, Petra Bakker, Carolini Kaid, Mayana Zatz, Floris Foijer #, Oswaldo Keith Okamoto #

Abstract

VAMP (Vesicle-associated membrane protein)-associated protein B and C (VAPB) has been widely studied in neurodegenerative diseases such as ALS, but little is known about its role in cancer. Medulloblastoma is a common brain malignancy in children and arises from undifferentiated cells during neuronal development. Therefore, medulloblastoma is an interesting model to investigate the possible relationship between VAPB and tumorigenesis. Here we demonstrate that high VAPB expression in medulloblastoma correlates with decreased overall patient survival. Consistent with this clinical correlation, we find that VAPB is required for normal proliferation rates of medulloblastoma cells in vitro and in vivo. Knockout of VAPB (VAPBKO) delayed cell cycle progression. Furthermore, transcript levels of WNT-related proteins were decreased in the VAPBKO. We conclude that VAPB is required for proliferation of medulloblastoma cells, thus revealing VAPB as a potential therapeutic target for medulloblastoma treatment.

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