Mecanismos implicados en la diferenciación epidermoide y melanocítica en respuesta al daño en el ADN

Résumé

Lung epidermoid carcinoma and melanoma are aggressive tumours with difficult treatment. DNA damage-induced differentiation is an often disregarded antitumor protection of cells. This Thesis is focused on the study of DNA damage-induced differentiation in lung and mammary gland epithelial cells, and in skin melanocytes. Our study shows that the response of lung and mammary cells involves epidermoid cell transdifferentiation. This explains why epidermoid carcinoma is frequent in the lung (highly exposed to genotoxic agents) but very rare in the breast (more protected). Our results also show that oncogene-induced DNA damage triggers differentiation in melanocytes, in association with senescence. Both epidermoid metaplasia of lung cells and melanocyte differentiation in response to genetic damage constitute antitumor mechanisms preserving tissue cellularity and functionality. Thus, this Thesis provides new insight into the origin of melanoma and epidermoid carcinoma in non-epidermoid tissues like the lung.