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Étude de l'impact de l'activité traductionnelle sur le phénotype tumoral dans le cancer du côlon

Abstract : Despite significant advances in diagnostics and treatment, colorectal cancer (CRC) remains a major cause of mortality worldwide and occurrence of metastasis represents the primary cause of death. Metastasis process, chemoresistance and tumor recurrence is powered by a minor subpopulation of tumor cells endowed with self‐renewal and multi‐lineage differentiation ability: the cancer stem cells (CSC).Translation of mRNA into protein is the final step in gene-expression process, which mediates the formation of the translatome from genomic information. Several mechanisms, such as signaling pathways, translation factors availability, alternative open reading frame and alternative initiation pathways account for real time translatome remodeling. Moreover, an emerging concept suggests that ribosome is heterogeneous and can be "reprogrammed". These "specialized ribosomes" would preferentially engage certain mRNA at the expense of others and therefore drive cell phenotype and favor cell adaptation. Many studies have correlated deregulation of both translation machinery composition and activity with cancer initiation and evolution. From that perspective, CSC might well represent a perfect model to test whether the translation apparatus takes an active part in tumor initiation, progression, and metastasis. Our goal is to demonstrate that protein synthesis is differentially regulated depending on cancer cell subpopulation and determine whether ribosomal heterogeneity could influence tumoral evolution and plasticity. In a long run, we envision the development of novel therapies based on specific targeting of translational control in CSC.
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Laura Yazdani. Étude de l'impact de l'activité traductionnelle sur le phénotype tumoral dans le cancer du côlon. Médecine humaine et pathologie. Université Montpellier, 2017. Français. ⟨NNT : 2017MONTT031⟩. ⟨tel-01684226⟩

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