Detecting autophagy in response to ER stress signals in cancer.
Different physiological and pathological situations that produce alterations in the endoplasmic reticulum, lead to a condition known as ER stress. ER stress activates a complex intracellular signal transduction pathway, called unfolded protein response (UPR). UPR is tailored essentially to reestablish ER homeostasis. However, when persistent, ER stress can switch the cytoprotective functions of UPR into cell death promoting mechanisms. One of the cellular mechanisms that are regulated by ER stress is autophagy. Autophagy is a cellular process by which different cytoplasmic components including organelles are targeted for degradation to the autophagosomes. Interestingly, like ER stress, autophagy can be a protective or a cell death promoting mechanism. Recently, a variety of anticancer therapies (including those that stimulate ER stress) have been shown to activate autophagy in tumor cells, which has been proposed to either enhance cancer cell death or act as a mechanism of resistance to chemotherapy. In this chapter, we will describe some of the procedures that are currently used to analyze autophagy as well as some of the experimental approaches that can be undertaken to investigate the connection between ER stress and autophagy in cancer.
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
María
M
Salazar
Sonia
S
Hernández-Tiedra
Sofía
S
Torres
Mar
M
Lorente
Manuel
M
Guzmán
Guillermo
G
Velasco
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000473:pathology / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008869:Microtubule-Associated Proteins / Q000502:physiology; D046912:Multiprotein Complexes; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases; D014183:Transplantation, Heterologous; D056811:Unfolded Protein Response
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases