Journal Article

Identification of the tumour transition states occurring during EMT

Boumahdi, Soufiane, Minguijón, Esmeralda, Balsat, Cédric, Sotiropoulou, Panagiota A., Fioramonti, Marco, Brisebarre, Audrey, Dubois, Christine, Sifrim, Alejandro, Lanas, Angel, Revenco, Tatiana, Van Keymeulen, Alexandra, De Clercq, Sarah, Scozzaro, Samuel, Brown, Daniel, De Cock, Florian, D’Haene, Nicky, Pastushenko, Ievgenia, Sokolow, Youri, Salmon, Isabelle, Blanpain, Cédric, Moers, Virginie, Sopena, Federico, Marine, Jean-Christophe, Voet, Thierry, Lemaire, Sophie

2018

Overview

In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states. Epithelial-to-mesenchymal transition in tumour cells occurs through distinct intermediate states, associated with different metastatic potential, cellular properties, gene expression, and chromatin landscape

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 14/1 / 14/34 / 14/63 / 38/77 / 38/88 / 38/90 / 38/91 / 631/67/2329 / 631/67/327 / 64 / 64/110 / 64/60 / Animals / Bioinformatics / Cancer / Cancer metastasis / Cell surface / Chromatin / Chromatin - genetics / DNA binding proteins / Epigenesis, Genetic / Epigenetic inheritance / Epithelial Cells - metabolism / Epithelial Cells - pathology / Epithelial-Mesenchymal Transition - genetics / Female / Gene expression / Gene Expression Regulation, Neoplastic / Gene Regulatory Networks / Genes / Health aspects / Humanities and Social Sciences / Humans / Invasiveness / Male / Mammary Neoplasms, Animal - genetics / Mammary Neoplasms, Animal - pathology / Mesenchyme / Mesoderm - metabolism / Mesoderm - pathology / Metastases / Metastasis / Mice / multidisciplinary / Neoplasm Invasiveness - genetics / Neoplasm Invasiveness - pathology / Neoplasm Metastasis - genetics / Neoplasm Metastasis - pathology / Neoplasms - genetics / Neoplasms - pathology / Pancreatic cancer / Plastic foam / Principal components analysis / Science / Science (multidisciplinary) / Signal Transduction / Skin / Skin Neoplasms - genetics / Skin Neoplasms - pathology / Stem cells / Subpopulations / Surface markers / Transcription (Genetics) / Transcription factors / Transcription, Genetic / Transportation networks / Tumors