DYRK1A activates NFATC1 to increase glioblastoma migration

We found that DYRK1A protein was positively correlated with that of NFATc1 through affecting NFATc1  degradation and transactivation in GBM cells. DYRK1A inhibition or polypeptide derived from DYRK1A-targeted motif of NFATc1, clearly destabilized NFATc1 protein and impaired glioblastoma migration. We propose that the recovery of NFATc1 stability is a key oncogenic event in a large proportion of gliomas and polypeptide pharmacological inhibition of DYRK1A could represent a promising therapeutic intervention for NFATc1-dependent GBM. AbstractGlioblastoma (GBM) is the most aggressive glioma, and is prone to develop resistance to chemotherapy and radiotherapy; hence, patients with glioblastoma have a high recurrence  rate and a low 1-year survival rate. In addition, the pathogenesis of glioblastoma is complex and largely unknown, and the available treatments are limited. Here, we uncovered a fundamental role of DYRK1A in regulating NFATC1 in GBMs. We found that DYRK1A was highly expressed in glioma and g lioblastoma cells, and its expression was positively correlated with that of NFATC1. Moreover, inhibition of DYRK1A promoted NFATC1 degradation in GBM cells and sharply reduced the transactivation of NFATC1, not only by decreasing the expression of NFATC1-targeted genes, but also by reducing the lu ciferase activity, and vice versa. However, DYRK1A had the opposite effect on NFATC2. Most importantly, our data suggest that DYRK1A inhibition reduces glioblastoma migration...

Source: Cancer Medicine - July 26, 2021 Category: Cancer & Oncology Authors: Heng Liu, Qian Sun, Shuai Chen, Long Chen, Wenming Jia, Juan Zhao, Xiulian Sun Tags: RESEARCH ARTICLE Source Type: research