Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.
| dc.contributor.author | Kadur Lakshminarasimha Murthy, Preetish | |
| dc.contributor.author | Xi, Rui | |
| dc.contributor.author | Arguijo, Diana | |
| dc.contributor.author | Everitt, Jeffrey I | |
| dc.contributor.author | Kocak, Dewran D | |
| dc.contributor.author | Kobayashi, Yoshihiko | |
| dc.contributor.author | Bozec, Aline | |
| dc.contributor.author | Vicent, Silvestre | |
| dc.contributor.author | Ding, Shengli | |
| dc.contributor.author | Crawford, Gregory E | |
| dc.contributor.author | Hsu, David | |
| dc.contributor.author | Tata, Purushothama Rao | |
| dc.contributor.author | Reddy, Timothy | |
| dc.contributor.author | Shen, Xiling | |
| dc.date.accessioned | 2024-02-01T17:58:08Z | |
| dc.date.available | 2024-02-01T17:58:08Z | |
| dc.date.issued | 2022-02 | |
| dc.description.abstract | Oncogenic Kras induces a hyper-proliferative state that permits cells to progress to neoplasms in diverse epithelial tissues. Depending on the cell of origin, this also involves lineage transformation. Although a multitude of downstream factors have been implicated in these processes, the precise chronology of molecular events controlling them remains elusive. Using mouse models, primary human tissues, and cell lines, we show that, in Kras-mutant alveolar type II cells (AEC2), FOSL1-based AP-1 factor guides the mSWI/SNF complex to increase chromatin accessibility at genomic loci controlling the expression of genes necessary for neoplastic transformation. We identified two orthogonal processes in Kras-mutant distal airway club cells. The first promoted their transdifferentiation into an AEC2-like state through NKX2.1, and the second controlled oncogenic transformation through the AP-1 complex. Our results suggest that neoplasms retain an epigenetic memory of their cell of origin through cell-type-specific transcription factors. Our analysis showed that a cross-tissue-conserved AP-1-dependent chromatin remodeling program regulates carcinogenesis. | |
| dc.identifier | S1534-5807(22)00006-5 | |
| dc.identifier.issn | 1534-5807 | |
| dc.identifier.issn | 1878-1551 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Elsevier BV | |
| dc.relation.ispartof | Developmental cell | |
| dc.relation.isversionof | 10.1016/j.devcel.2022.01.006 | |
| dc.rights.uri | ||
| dc.subject | Cell Line | |
| dc.subject | Nucleosomes | |
| dc.subject | Epithelial Cells | |
| dc.subject | Animals | |
| dc.subject | Mice, Inbred NOD | |
| dc.subject | Humans | |
| dc.subject | Mice, SCID | |
| dc.subject | Neoplasms | |
| dc.subject | Proto-Oncogene Proteins c-fos | |
| dc.subject | Transcription Factor AP-1 | |
| dc.subject | Cell Proliferation | |
| dc.subject | Organ Specificity | |
| dc.subject | Epigenesis, Genetic | |
| dc.subject | Base Sequence | |
| dc.subject | Mutation | |
| dc.subject | Oncogenes | |
| dc.subject | Proto-Oncogene Proteins p21(ras) | |
| dc.subject | Mutant Proteins | |
| dc.subject | Cell Plasticity | |
| dc.subject | Alveolar Epithelial Cells | |
| dc.subject | Epigenome | |
| dc.title | Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Everitt, Jeffrey I|0000-0003-0273-6284 | |
| duke.contributor.orcid | Crawford, Gregory E|0000-0001-6106-2772 | |
| duke.contributor.orcid | Tata, Purushothama Rao|0000-0003-4837-0337 | |
| duke.contributor.orcid | Reddy, Timothy|0000-0002-7629-061X | |
| duke.contributor.orcid | Shen, Xiling|0000-0002-4978-3531 | |
| pubs.begin-page | 310 | |
| pubs.end-page | 328.e9 | |
| pubs.issue | 3 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Biostatistics & Bioinformatics | |
| pubs.organisational-group | Cell Biology | |
| pubs.organisational-group | Molecular Genetics and Microbiology | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Pediatrics | |
| pubs.organisational-group | Medicine, Pulmonary, Allergy, and Critical Care Medicine | |
| pubs.organisational-group | Pediatrics, Medical Genetics | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Regeneration Next Initiative | |
| pubs.organisational-group | Biostatistics & Bioinformatics, Division of Integrative Genomics | |
| pubs.publication-status | Published | |
| pubs.volume | 57 |
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