E2 activates IGF-1R/PI3K and its downstream signals, Akt and JNK to promote cell growth. Simultaneously, E2 activates endoplasmic reticulum stress which activates a set of signaling pathways including three sensors (PERK, IRE1α, and ATF6), inflammatory responses, caspase 4/12, and adenosine monophosphate (AMP)-activated protein kinase (AMPK). The AMPK and Akt converge on mTOR with opposing regulatory effects to coordinate bioenergetics and cell viability. IRE1α and ATF6 are involved in the degradation of Akt.