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• W4386895351 abstract "Abstract Mesenchymal plasticity has been extensively described in advanced and metastatic epithelial cancers; however, its functional role in malignant progression, metastatic dissemination and therapy response is controversial. More importantly, the role of epithelial mesenchymal transition (EMT) and cell plasticity in tumor heterogeneity, clonal selection and clonal evolution is poorly understood. Functionally, our work clarifies the contribution of EMT to malignant progression and metastasis in pancreatic cancer. We leveraged ad hoc somatic mosaic genome engineering, lineage tracing and ablation technologies and dynamic genetic reporters to trace and ablate tumor-specific lineages along the phenotypic spectrum of epithelial to mesenchymal plasticity. The experimental evidences clarify the essential contribution of mesenchymal lineages to pancreatic cancer evolution and metastatic dissemination. Spatial genomic analysis combined with single cell transcriptomic and epigenomic profiling of epithelial and mesenchymal lineages reveals that EMT promotes with the emergence of chromosomal instability (CIN). Specifically tumor lineages with mesenchymal features display highly conserved patterns of genomic evolution including complex structural genomic rearrangements and chromotriptic events. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross species analysis of pancreatic and other human epithelial cancers. Mechanistically, we discovered that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, which in turn results in delayed mitosis and catastrophic cell division. Therefore, EMT favors the emergence of high-fitness tumor cells, strongly supporting the concept of a cell-state, lineage-restricted patterns of evolution, where cancer cell sub-clonal speciation is propagated to progenies only through restricted functional compartments. Restraining those evolutionary routes through genetic ablation of clones capable of mesenchymal plasticity and extinction of the derived lineages completely abrogates the malignant potential of one of the most aggressive form of human cancer." @default.
• W4386895351 created "2023-09-21" @default.
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• W4386895351 date "2023-09-19" @default.
• W4386895351 modified "2023-10-17" @default.
• W4386895351 title "Evolutionary fingerprints of EMT in pancreatic cancers" @default.
• W4386895351 cites W1497915798 @default.
• W4386895351 cites W1919257374 @default.
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• W4386895351 cites W1972091439 @default.
• W4386895351 cites W1972476556 @default.
• W4386895351 cites W1975032719 @default.
• W4386895351 cites W1994772304 @default.
• W4386895351 cites W2010873488 @default.
• W4386895351 cites W2014691022 @default.
• W4386895351 cites W2019214567 @default.
• W4386895351 cites W2023560061 @default.
• W4386895351 cites W2058172887 @default.
• W4386895351 cites W2066135299 @default.
• W4386895351 cites W2076583198 @default.
• W4386895351 cites W2080812145 @default.
• W4386895351 cites W2104135721 @default.
• W4386895351 cites W2107292147 @default.
• W4386895351 cites W2140916263 @default.
• W4386895351 cites W2146005104 @default.
• W4386895351 cites W2150322923 @default.
• W4386895351 cites W2152061559 @default.
• W4386895351 cites W2154283358 @default.
• W4386895351 cites W2154790710 @default.
• W4386895351 cites W2157923000 @default.
• W4386895351 cites W2171892226 @default.
• W4386895351 cites W2235737683 @default.
• W4386895351 cites W2531887049 @default.
• W4386895351 cites W2571183003 @default.
• W4386895351 cites W2586537166 @default.
• W4386895351 cites W2727977279 @default.
• W4386895351 cites W2733398634 @default.
• W4386895351 cites W2767749844 @default.
• W4386895351 cites W2785043177 @default.
• W4386895351 cites W2800392236 @default.
• W4386895351 cites W2817838603 @default.
• W4386895351 cites W2901068426 @default.
• W4386895351 cites W2913877697 @default.
• W4386895351 cites W2914759417 @default.
• W4386895351 cites W2915459742 @default.
• W4386895351 cites W2924124844 @default.
• W4386895351 cites W2952109315 @default.
• W4386895351 cites W2955641089 @default.
• W4386895351 cites W2967177832 @default.
• W4386895351 cites W2971488563 @default.
• W4386895351 cites W2984472267 @default.
• W4386895351 cites W3002770500 @default.
• W4386895351 cites W3004584205 @default.
• W4386895351 cites W3005469082 @default.
• W4386895351 cites W3011562658 @default.
• W4386895351 cites W3016718031 @default.
• W4386895351 cites W3023801326 @default.
• W4386895351 cites W3128607514 @default.
• W4386895351 cites W3159756629 @default.
• W4386895351 cites W3200323540 @default.
• W4386895351 cites W3206184033 @default.
• W4386895351 cites W3212093805 @default.
• W4386895351 cites W3215852532 @default.
• W4386895351 cites W4200559225 @default.
• W4386895351 cites W4214569871 @default.
• W4386895351 cites W4214876469 @default.
• W4386895351 cites W4225529913 @default.
• W4386895351 cites W4282980285 @default.
• W4386895351 cites W4285087726 @default.
• W4386895351 cites W4296293070 @default.
• W4386895351 cites W4307658844 @default.

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