Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity

• DOI: 10.1126/sciadv.adi1736
• Publication Date: 2024-02-14T18:58:58Z
• Authors: Hadrien De Blander; Laurie Tonon; Frédérique Fauvet; Roxane M. Pommier; Christelle Lamblot; Rahma Benhassoun; Francesca Angileri; Benjamin Gibert; Raphaël Rodriguez; Maria Ouzounova; Anne-Pierre Morel; Alain Puisieux
• Keywords: Reprogramming; Malignant Transformation; Senescence; Tumor progression

In breast cancers, aberrant activation of the RAS/MAPK pathway is strongly associated with mesenchymal features and stemness traits, suggesting an interplay between this mitogenic signaling epithelial-to-mesenchymal plasticity (EMP). By using inducible models human mammary epithelial cells, we demonstrate herein that oncogenic RAS promotes ZEB1-dependent EMP, which necessary for malignant transformation. Notably, EMP triggered by secretion pro-inflammatory cytokines from neighboring RAS-activated senescent a prominent role IL-6 IL-1α. Our data contrast common view cellular senescence as tumor-suppressive mechanism process promoting late stages tumor progression in response to signals microenvironment. We highlighted here pro-tumorigenic cooperation leverages on oncogene-induced trigger reprogramming