Consistent with previous reports [30, 31], in the present study, we demonstrate that GSK-3β directly phosphorylates 4EBP1 independent of rapamycin sensitivity to mTORC1 and continuously activates 4EBP1 and S6K, the mTORC1 downstream substrates to drive cell proliferation in RCC cell lines. Here, RPS6KB1 is linked to renal cell carcinoma.