Instead, the Warburg effect is an essential characteristic of metabolic reprogramming, resulting from the interplay between (normoxic/hypoxic) hypoxia-inducible factor-1α (HIF-1α) overexpression, oncogene activation (cMyc, Ras), loss of function of tumor suppressors (mutant p53, mutant phosphatase and tensin homolog (PTEN), microRNAs and sirtuins with suppressor functions), activated (PI3K–Akt–mTORC1, Ras–Raf–MEK–ERK–cMyc, Jak–Stat3) or deactivated (LKB1–AMPK) signaling pathways, components of the tumor microenvironment, and HIF-1α cooperation with epigenetic mechanisms [65,66]. Here, PTEN is linked to neoplasm.