AURKB and PI3K/AKT/mTOR pathways converge to regulate TERT expression

Abstract Telomere length maintenance, critical for cancer progression, can be driven by TERT promoter mutations (TERTpMUT), which are markers of poor prognosis across multiple cancers. Their tumor-specificity also makes them attractive chemotherapeutic targets. Here, we identified previously uncharacterized pathways regulating TERTpMUT activity by inserting a luciferase reporter downstream of TERTpMUT in SW1736 anaplastic thyroid cancer cells via CRISPR-Cas9, generating SW1736TERT/LUC, and screening a 218-kinase inhibitor library. Beyond MAPK regulation, we found co-regulatory roles for PI3K/AKT/mTOR1 signaling and the cell cycle