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Identification des régulateurs de l’expression transcriptionnelle de TSPAN8 impliqués dans l’invasion précoce du mélanome cutané

Abstract : Cutaneous melanoma is the deadliest skin condition. Curing this cancer requires an early diagnosis and surgical excision of the non-invasive primary lesions. Indeed, patients with metastasis have few chances to survive this cancer since the melanoma lesions rapidly develop treatment resistances, and can disseminate metastasis in numerous organs. Crossing the skin basal membrane called the dermal epidermal junction is the first crucial step of early melanoma invasion. Our team has studied the early invasion of melanoma for many years, and demonstrated for the first time the implication of Tetraspanin (TSPAN8) in melanoma early invasion. Indeed, the expression of this gene and the protein that it codes appears with the progression of melanoma and confers the tumor cells an invasive phenotype. Several members of the tetraspanin protein family are known for their implication in various cancers, yet their transcriptional regulation remains poorly understood. In the case of TSPAN8, nothing was known regarding its transcriptional regulation in melanoma. The experiments presented in this thesis allowed us to identify the first known regulators of TSPAN8 transcriptional expression, and also to begin the functional study of the regulators impact on TSPAN8 dependent invasion of human cutaneous melanoma. Amongst these regulators are the member of the Mediator Complex MED19/LCMR1 and the tumor suppressor p53. The results presented in the present manuscript allow a better understanding of cutaneous melanoma early invasion and should help improving the treatments against this cancer in the future
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https://tel.archives-ouvertes.fr/tel-01665491
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Gweltaz Agaësse. Identification des régulateurs de l’expression transcriptionnelle de TSPAN8 impliqués dans l’invasion précoce du mélanome cutané. Biologie cellulaire. Université de Lyon, 2016. Français. ⟨NNT : 2016LYSE1279⟩. ⟨tel-01665491⟩

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