On the other hand, cell-extrinsic microenvironmental factors such as nutrient availability, hypoxia, chemokines, growth factors and their receptors promote tumor growth through the activation of specific signal transduction pathways including PI3K/AKT/mTOR signaling, AMP-activated protein kinase (AMPK) signaling, Hedgehog signaling, calcineurin/nuclear factors of activated T-cells (NFAT) signaling, Wnt signaling and hypoxia-inducible factor (HIF-1) signaling. Here, HIF1A is linked to neoplasm.