DYRK1A activates NFATC1 to increase glioblastoma migration

Abstract

Glioma is the most common brain cancer, and high-grade gliomas, including glioblastoma multiforme (GBM), are the most aggressive types of glioma. 1 The current standard treatment for GBM involves surgical resection followed by the administration of an alkylating agent, temozolomide, both concurrent with and after radiotherapy. Bevacizumab is administered as a second-line treatment after relapse. 2,3 However, GBM is resistant to chemotherapy and radiotherapy, with a median patient survival time of approximately one year. 1,4 The highly invasive nature of GBM cells is thought to contribute to the poor prognosis of this tumor, necessitating the exploration of alternative therapies. Many factors are involved in the migration and invasion of malignant tumors, including the nuclear factor of activated T cells (NFAT). [5][6][7] NFAT, originally found in activated T cells, is a transcription factor that induces gene transcription during the immune response. 8 The NFAT transcription factor family consists of five members: NFAT1 (NFATC2, NFATp),

DYRK1A reinforces epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma via cooperatively activating STAT3 and SMAD

“…Several studies have indicated that DYRK1A acts as a tumour suppressor gene, while others have highlighted its pro-oncogenic activity [ 8 ]. For instance, DYRK1A could activate NFATC1 to increase the migration ability of glioblastoma cells, while it could play an important role in maintaining cancer stemness in oral squamous cell carcinoma [ 15 , 33 ]. In contrast, another study showed that DYRK1A could act as a tumour suppressor by downregulating c-Myc in acute myeloid leukaemia cells [ 34 ].…”

“…However, the binding sites of between DYRK1A and TSC1 should be further determined. It has been reported that DYRK1A increases the stability of its substrates, such as NFATC1, by phosphorylating and interfering with their ubiquitin-mediated proteasomal degradation [ 15 ]. Our data indicated that DYRK1A enhanced the expression of TSC1 and that TSC1 enhanced the expression of DYRK1A.…”

“…A study demonstrated that DYRK1A positively regulated VEGF-dependent nuclear factor of activated T cells (NFAT) transcriptional responses in endothelial cells and was involved in angiogenesis [ 14 ]. In addition, DYRK1A enhanced the migration ability of glioblastoma cells by activating NFATC1 in vitro [ 15 ]. Although current evidence has highlighted the importance of DYRK1A in tumour metastasis, its promoting effects on tumour metastasis, as well as the underlying mechanism, need further investigation.…”

Chemical, Biochemical, Cellular, and Physiological Characterization of Leucettinib-21, a Down Syndrome and Alzheimer’s Disease Drug Candidate

“…Given the literature supporting the link between DYRK1A inhibition and induction of glioblastoma cell death ,− (see the review in ref ) and given the relative brain permeability of Leucettinib-21 ( 4 ) (unpublished results), we tested this compound and its kinase-inactive isomer on patient-derived, Temozolomide-resistant glioblastoma stem-like cells (GSCs) (Figure ). Cells were exposed for 48 h to a range of concentrations of both compounds, and cell death was assessed using the Cell Titer-Glo luminescent ATP assay.…”

Systematic analysis identifies REST as an oncogenic and immunological biomarker in glioma

“…The validation was approved by the Ethics Committee of Qilu Hospital, and all patients provided informed consent. IHC staining was performed as previously described 30 . Serial sections of formalin-fixed tissues were deparaffinized, rehydrated, immersed in citrate buffer (pH 6.0), and microwaved for 15 min to retrieve antigens.…”