In the team “Initiation of Epithelial Cancers”, we are working since 2002 on how the molecular mechanisms of cellular senescence impact on neoplastic transformation. Our main activities are basic research aiming at understanding the basics of cell senescence, especially that of epithelial cells that are poorly studied compared to fibroblastic models, although much more relevant to cancer.

For that purpose, we use in vitro cultured models of normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). Both recapitulate cellular aging (senescence) in response to normal replication and various inducers. Moreover, we also established that NHEKs recapitulate the early events of cellular transformation in culture. Therefore, we hope to decipher the mechanisms explaining why these two cell types are differently prone to transform. To this end:

(i) we explore the role of oxidatively-induced DNA damage in both senescence and post-senescence neoplastic cells.

(ii) we also investigate the potential role of endoplasmic reticulum stress and autophagic activity in the outcome of senescent cells, i.e. cell death, irreversible senescence or neoplastic escape.

(iii) besides, we examine whether an alteration of the paracrine interactions between epidermis and dermis during aging could differently direct the outcome of each cell type

(iv) finally, we are also interested in the model of second cancers developing after radiotherapy, with the hypothesis that radiations could recapitulate some events occurring with normal aging.

Keywords: Cancer, epithelium, cell death, cell senescence, DNA damage, oxidative stress, endoplasmic reticulum stress, oncogenes and tumor suppressor genes