PKA activation increased hnRNP A1 methylation, while combined inhibition of PKA and mTOR reduced GBM cell viability, suppressed IRES-mediated translation, and induced apoptosis both in vitro and in intracranial xenografts.<h4>Conclusions</h4>These findings identify a PKA/PRMT5/hnRNP A1 signaling axis that promotes IRES-dependent translation and contributes to mTOR inhibitor resistance in GBM. Here, MTOR is linked to glioblastoma.