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Etude du rôle des protéines QSOX1 et GABARAPL1 dans l'autophagie et le cancer

Abstract : The aim of my thesis was to study the role of QSOX1 and GABARAPL1 (GL1) in autophagy and cancer. QSOX1 protein has been shown to be involved in the regulation of protein folding and is associated with protection against cellular stress and cancer. Given the function of QSOX1 in stress and cancer, two processes which have been previously linked to autophagy, we have studied the role of QSOX1 in autophagy. We showed that QSOX1 protein can maintain cellular homeostasis during amino acids starvation. Our results also indicated that QSOX1 inhibits autophagy through the inhibition of autophagosome/lysosome fusion which could explain the role of QSOX1 on cell invasion. The GL1 protein, belonging to the ATG8 family and GABARAP subfamily, is associated with autophagosomes during autophagy and have a tumor suppressor role. Given the function of GL1 in cancer and autophagy, we aimed to characterize the role of GL1 in autophagy and determine whether GL1 conjugation to autophagosomes is necessary for its tumor suppressive functions. Our results demonstrated that GL1 presents different regulatory functions during early and later stages of autophagy. Sorne of these functions seem to be independent of its conjugation to autophagosomes. Interestingly, GLl tumor suppressive function appeared independent of its conjugation to autophagosomes. Our results also demonstrated that GL1 play an important role in the regulation of metabolism and mitochondrial homeostasis through autophagy, function which could explain its role in cancer. Together, this work allowed us to establish a link between autophagy, cellular stress, metabolism and cancer
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Laura Poillet Perez. Etude du rôle des protéines QSOX1 et GABARAPL1 dans l'autophagie et le cancer. Cancer. Université de Franche-Comté, 2015. Français. ⟨NNT : 2015BESA3020⟩. ⟨tel-01689980⟩

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