The role of Endoplasmic Reticulum Stress and Autophagy in the mechanisms of resistance and cancer development: a review of previous reports and new data

ANSELMINO, LUCIANO; RICHARD SM; MARTINEZ MARIGNAC VERONICA

Workshop; ICGEB Workshop: Autophagy: physiological and pathological role; 2016

Autophagy has been postulated to play a role in breast and colorectal cancer (CRC) developmental, cancer therapy resistance and recurrence in other types of cancer (lymphomas and leukemias). The aim of the present project is to understand the signalling events associated with acquired resistance to a tyrosin and src kinase family inhibitor (TKI), Dasatinib, in triple negative basal-like cell lines, primary cell of chronic lymphocytic leukemia patients (CLL) and AOM/DSS induced colorectal cancer in mouse in an attempt to determine the effect of autophagy and detect a novel, molecularly targeted therapy for these cancers. Dr. Martinez Marignac and collaborators have determined the phenotypic consequences of sustained exposure to Dasatinib in BT20 and MDA MB231 breast cancer cell lines (DOI: 10.18632/oncotarget.8146, 2016) as well as she have reported the effect of Dasatinib administration on primary leukemic cell and the subsequent conformation of two therapeutic subpopulations based on bioenergetic (catabolic or anabolic metabolism) organization display by chronic lymphocytic leukemia (CLL) patients (DOI: 10.18632/oncotarget.1508, 2013).As Transmission Electron Microscopy (TEM) is extremely useful for visualizing subcellular compartments, intracellular organelles and cytoskeleton at high spatial resolution we have made use of the technique to determine ultrastructural changes in a induced model of colorectal cancer in mouse. Autophagy was first detected by TEM in the 1950s and it was originally observed as focal degradation of cytoplasmic areas performed by lysosomes. An animal model with more than 10 year of use for the study of colorectal cancer (CRC) is the induction of CRC by the administration of azoximethane (AOM) and dextran sodium sulfate (DSS). Our goal was to evaluate murine intestine tissue at week 0 of AOM/DSS induction and week 20 of the induction process and visualized ultra structural changes and create our AOM/DSS CRC Atlas.