Défense de thèse de doctorat en sciences
Implication de la protéine TMEM45A dans la chimiorésistance
Date : 27/03/2019 16:00 - 27/03/2019 18:00
Lieu : Auditoire L22, Faculté de Philosophie et Lettres, 2e étage, 1 rue Grafé, 5000 Namur
Orateur(s) : Kathleen SCHMIT
Organisateur(s) : Carine MICHIELS
Jury
Poumay Yves (UNamur), président; Michiels Carine (UNamur), secrétaire; Noel Agnès (ULiège); Graux Carlos (CHU UCL UNamur); Gillet Jean-Pierre (UNamur).
Résumé
Successful remission can be achieved with chemotherapy in most cases of cancer but refractory diseases and relapses remain a major obstacle. Resistance to treatment can appear by intrinsic adaptation of cancer cells themselves but also by features of the tumor microenvironment, and more specifically hypoxia (1% O2). In this condition, the transcription factor HIF-1 is stabilized leading to the transcription of several target genes such as TMEM45A. The aim of the project is to pursue the study of the contribution of this protein in modulating the responses to treatment and of the mechanisms by which it acts.
The role of TMEM45A in the resistance to chemotherapy has been studied in two models: head and neck squamous cell carcinoma (SQD9 cells) and renal cell carcinoma (RCC4 plus pVHL). TMEM45A influences the drug sensitivity of cancer cells depending on the cancer type through a modulation of cisplatin-activation of UPR pathway leading to the resistance of RCC4 plus pVHL cells, whereas it increased SQD9 cell sensitivity to cisplatin through the deregulation of cell responses to cisplatin-induced DNA damage. Furthermore, this protein seems to be involved in tumor growth in vivo. Altogether our data emphasize the involvement of TMEM45A in tumor aggressiveness and suggest that TMEM45A might be used as a marker of patient responses to treatment.
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