Collectively these data argue that [sorafenib + sildenafil] treatment promotes autophagosome formation in cancer cells through multiple inter-locking mechanisms: decreased chaperone function resulting in elevated ATG13 phosphorylation and ER stress –stimulated expression of Beclin1 and ATG13; and altered PP1c association with eIF2α and ATG13 which acts to maintain these signals. The gene discussed is EIF2A; the disease is cancer.