Role of miR-200 and stromal heterogeneity in ovarian and breast tumours

Orateur : Fatima MECHTA-GRIGORIOU (Institut Curie - Inserm U830, PARIS)

In last years, we demonstrated that a chronic oxidative stress accelerates aging (Laurent, Cell Metabolism, 2008) and increases metastatic spread, by deeply modifying tumor microenvironment (Toullec, EMBO Mol Med, 2010 ; Costa, Sem Cancer Biol, 2014). However, while oxidative stress increases tumour development, it can also improve response to chemotherapy of ovarian cancer patients, in particular to Taxanes (Mateescu, Nat Med, 2011 ; Batista, Nat Commun, 2016). Moreover, autophagy, cellular process well-known to circumvent intracellular stresses, helps tumour cells from triple-negative breast cancer patients to escape from chemotherapy (Lefort, Autophagy, 2014). Thus, oxidative stress promotes tumorigenesis but improves chemosensitivity, defining the paradoxical effect of Reac0ve Oxygen Species. Altogether, our data have deciphered the pros and cons of intracellular oxidative stress and activation of downstream signalling pathways, such as MEK/ERK, with immediate translational applications for cancer patients (Gruosso, Nat Commun, 2015 ; Gruosso, EMBO Mol Med, In press). Finally, in the last years, using various approaches including flow cytometry on fresh human tissues, immunohistochemistry combined to automated image analysis and functional assays, we have identified 4 different subpopulations of carcinoma-associated fibroblasts in human breast and ovarian carcinomas. We are currently investigating their signatures and functions in tumour development and progression.

Télécharger dans mon agenda