Nucleoporin TPR (translocated promoter region, nuclear basket protein) upregulation alters MTOR-HSF1 trails and suppresses autophagy induction in ependymoma

Children with ependymoma have high mortality rates because ependymoma is resistant to conventional therapy. Genomic and transcriptomic studies have identified potential targets as significantly altered genes in ependymoma patients. Although several candidate oncogenes in ependymoma were recently reported, the detailed mechanisms for the roles of these candidate oncogenes in ependymoma progression remain unclear. Here, we report an oncogenic role of the nucleoporin TPR (translocated promoter region, nuclear basket protein) in regulating HSF1 (heat shock transcription factor 1) mRNA trafficking, maintaining MTORC1 activity to phosphorylate ULK1, and preventing macroautophagy/autophagy induction in ependymoma. High expression of TPR were associated with increased HSF1 and HSPA/HSP70 expression in ependymoma patients. In an ependymoma mouse xenograft model, MTOR inhibition by rapamycin therapeutically suppressed TPR expression and reduced tumor size in vivo. Together, these results suggest that TPR may act as a biomarker for ependymoma, and pharmacological interventions targeting TPR-HSF1-MTOR may have therapeutic potential for ependymoma treatment.

Automated summary

Children with ependymoma face high mortality rates due to resistance to conventional therapy. Targeting the oncogenic role of TPR in regulating HSF1 and MTOR signaling pathways may serve as a potential therapeutic approach for ependymoma treatment. TPR expression levels could potentially act as a biomarker for ependymoma, with pharmacological interventions showing promise in reducing tumor size in vivo.