An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530)
R Y-J Huang,Meng Kang Wong,Tuan Zea Tan,K.T. Kuay,A H C Ng,Vin Yee Chung,Y-S Chu,Noriomi Matsumura,H-C Lai,Y F Lee,W-J Sim,C Chai,E Pietschmann,Seiichi Mori,Seiichi Mori,Jeffrey Low,Mahesh Choolani,Jean Paul Thiery,Jean Paul Thiery +18 more
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It is shown how a 33-gene EMT Signature can sub-classify an OC cohort into four EMT States correlating with progression-free survival (PFS) and concluded that the characterisation of intermediate EMT states provides a new approach to better define EMT.Abstract:
The phenotypic transformation of well-differentiated epithelial carcinoma into a mesenchymal-like state provides cancer cells with the ability to disseminate locally and to metastasise Different degrees of epithelial–mesenchymal transition (EMT) have been found to occur in carcinomas from breast, colon and ovarian carcinoma (OC), among others Numerous studies have focused on bona fide epithelial and mesenchymal states but rarely on intermediate states In this study, we describe a model system for appraising the spectrum of EMT using 43 well-characterised OC cell lines Phenotypic EMT characterisation reveals four subgroups: Epithelial, Intermediate E, Intermediate M and Mesenchymal, which represent different epithelial–mesenchymal compositions along the EMT spectrum In cell-based EMT-related functional studies, OC cells harbouring an Intermediate M phenotype are characterised by high N-cadherin and ZEB1 expression and low E-cadherin and ERBB3/HER3 expression and are more anoikis-resistant and spheroidogenic A specific Src-kinase inhibitor, Saracatinib (AZD0530), restores E-cadherin expression in Intermediate M cells in in vitro and in vivo models and abrogates spheroidogenesis We show how a 33-gene EMT Signature can sub-classify an OC cohort into four EMT States correlating with progression-free survival (PFS) We conclude that the characterisation of intermediate EMT states provides a new approach to better define EMT The concept of the EMT Spectrum allows the utilisation of EMT genes as predictive markers and the design and application of therapeutic targets for reversing EMT in a selective subgroup of patientsread more
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Journal ArticleDOI
EMT Transition States during Tumor Progression and Metastasis.
TL;DR: The role of the transcriptional and epigenetic landscapes, gene regulatory network and their surrounding niche in controlling the transition through the different EMT states in cancer is summarized.
Journal ArticleDOI
Identification of the tumour transition states occurring during EMT
Ievgenia Pastushenko,Audrey Brisebarre,Alejandro Sifrim,Alejandro Sifrim,Marco Fioramonti,Tatiana Revenco,Soufiane Boumahdi,Alexandra Van Keymeulen,Daniel Brown,Virginie Moers,Sophie Lemaire,Sarah De Clercq,Esmeralda Minguijón,Cédric Balsat,Youri Sokolow,Christine Dubois,Florian De Cock,Samuel Scozzaro,Federico Sopena,Angel Lanas,Nicky D'Haene,Isabelle Salmon,Jean-Christophe Marine,Thierry Voet,Thierry Voet,Panagiota A. Sotiropoulou,Cédric Blanpain +26 more
TL;DR: A large panel of cell surface markers in skin and mammary primary tumours is screened, and the existence of multiple tumour subpopulations associated with different EMT stages are identified: from epithelial to completely mesenchymal states, passing through intermediate hybrid states.
Journal ArticleDOI
Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients.
Tuan Zea Tan,Qing Hao Miow,Yoshio Miki,Tetsuo Noda,Seiichi Mori,Ruby Yun-Ju Huang,Ruby Yun-Ju Huang,Jean Paul Thiery,Jean Paul Thiery +8 more
TL;DR: This universal and quantitative EMT scoring was used to establish an EMT spectrum across various cancers, with good correlation noted between cell lines and tumours, and it is demonstrated that mesenchymal‐like tumours do not always show resistance to chemotherapy.
Journal ArticleDOI
Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis
Mohit Kumar Jolly,Marcelo Boareto,Marcelo Boareto,Bin Huang,Dongya Jia,Mingyang Lu,Eshel Ben-Jacob,Eshel Ben-Jacob,José N. Onuchic,Herbert Levine +9 more
TL;DR: The operating principles of the core regulatory network for EMT/MET that acts as a “three-way” switch giving rise to three distinct phenotypes – E, M and hybrid E/M are reviewed and a theoretical framework that can elucidate the role of many other players in regulating epithelial plasticity is presented.
Journal ArticleDOI
Epithelial-Mesenchymal Plasticity in Cancer Progression and Metastasis
Wei Lu,Yibin Kang +1 more
TL;DR: The regulatory mechanisms and pathological roles of epithelial-mesenchymal plasticity are discussed, with a focus on recent insights into the complexity and dynamics of this phenomenon in cancer.
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TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
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