ER Stress & Autophagy in Cancer: Contenders or Partners in Crime?

Tumour development and progression are associated to a variety of events responsible for normal cell transformation, resulting in uncontrolled cell proliferation, tumour core formation, vascularization and, finally, tumour cell dissemination. Although oncogenic transformation represents the first episode responsible for tumour initiation, secondary events are also required to sustain cancer cell growth and survival, and inhibit cell death. ER stress and autophagy are two physiological pathways activated by cells under stress conditions, primarily to cope with stress and ensure cell survival, although unresolved or acute stress may shift pro-survival into pro-deathsignalling of both pathways. Since autophagy may represent a barrier against cell transformation, established tumours cells induce both autophagy and ER stress in response to metabolic stress to promote survival. Autophagy induction is also stimulated by the unfolded protein response (UPR) under ER stress conditions and, on the other hand, the former counterbalances ER expansion during the UPR, indicating a close and intricate mutual crossregulation, which is exploited by cancer cells to survive and inhibit death stimuli, such as those of chemotherapeutic drugs.