To clarify the apparent discordance between the activation of both mTOR and autophagy by PRL-3, we analysed the consequences of overexpressing EGFP-PRL-3 (PRL-3), EGFP-PRL-3-C104S (C104S; catalytic-inactive mutant), or empty EGFP vector (Vec) in nine human cancer cell lines from diverse cancer types. Here, PTP4A3 is linked to cancer.