IGF-1 exerts its effect through autocrine, paracrine, and endocrine mechanisms.35 IGF-1 plays an important role in tumorigenesis, angiogenesis, proliferation, and metastasis in various cancers.36,37 Studies have proven that the IGF-1/mTOR signaling pathway can facilitate cancer cell survival.38 The PI3K/AKT/mTOR pathway satisfies the metabolic demands for cancer proliferation, invasion and metastasis by allowing the utilization of amino acid substrates and one-carbon units.25 We demonstrate that the PI3K/AKT/mTOR pathway regulates ENO2 K394 deacetylation upon IGF-1 stimulation. Here, ENO2 is linked to cancer.