Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity
| Autor: | Purushothama Rao Tata, Daniel T. Montoro, Hongmei Mou, Ryan D. Chow, Jayaraj Rajagopal, Mari Mino-Kenudson, Lida P. Hariri, Leif W. Ellisen, Srinivas Vinod Saladi, Shioko Kimura, Arvind Konkimalla, Angela R. Shih, Anne Bara, Aleksandra Tata |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms Esophageal Neoplasms Cell Plasticity Thyroid Nuclear Factor 1 Cell Embryonic Development Biology Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences SOX2 Stomach Neoplasms medicine Animals Humans Cell Lineage Molecular Biology Mice Knockout SOXB1 Transcription Factors Endoderm Transdifferentiation Gene Expression Regulation Developmental Cell Differentiation Foregut Cell Biology respiratory system Prognosis Adenocarcinoma Mucinous Embryonic stem cell Epithelium Cell biology Mice Inbred C57BL Survival Rate 030104 developmental biology medicine.anatomical_structure Cancer cell Carcinoma Squamous Cell Respiratory epithelium Female Signal Transduction Developmental Biology |
| Zdroj: | Developmental Cell. 44:679-693.e5 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2018.02.024 |
| Popis: | We show that the loss or gain of transcription factor programs that govern embryonic cell-fate specification is associated with a form of tumor plasticity characterized by the acquisition of alternative cell fates normally characteristic of adjacent organs. In human non-small cell lung cancers, downregulation of the lung lineage-specifying TF NKX2-1 is associated with tumors bearing features of various gut tissues. Loss of Nkx2-1 from murine alveolar, but not airway, epithelium results in conversion of lung cells to gastric-like cells. Superimposing oncogenic Kras activation enables further plasticity in both alveolar and airway epithelium, producing tumors that adopt midgut and hindgut fates. Conversely, coupling Nkx2-1 loss with foregut lineage-specifying SOX2 overexpression drives the formation of squamous cancers with features of esophageal differentiation. These findings demonstrate that elements of pathologic tumor plasticity mirror the normal developmental history of organs in that cancer cells acquire cell fates associated with developmentally related neighboring organs. |
| Databáze: | OpenAIRE |
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