Emergence of a high-plasticity cell state during lung cancer evolution Journal Article
| Authors: | Marjanovic, N. D.; Hofree, M.; Chan, J. E.; Canner, D.; Wu, K.; Trakala, M.; Hartmann, G. G.; Smith, O. C.; Kim, J. Y.; Evans, K. V.; Hudson, A.; Ashenberg, O.; Porter, C. B. M.; Bejnood, A.; Subramanian, A.; Pitter, K.; Yan, Y.; Delorey, T.; Phillips, D. R.; Shah, N.; Chaudhary, O.; Tsankov, A.; Hollmann, T.; Rekhtman, N.; Massion, P. P.; Poirier, J. T.; Mazutis, L.; Li, R.; Lee, J. H.; Amon, A.; Rudin, C. M.; Jacks, T.; Regev, A.; Tammela, T. |
| Article Title: | Emergence of a high-plasticity cell state during lung cancer evolution |
| Abstract: | Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma. The diversity of transcriptional states increases over time and is reproducible across tumors and mice. Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS. Cellular states capable of promoting tumor progression and resisting therapies exist in heterogeneous tumors. Marjanovic et al. discover that a high-plasticity cell state common to mouse and human lung tumors drives cellular heterogeneity, is highly tumorigenic and drug resistant, and associates with poor patient prognosis. © 2020 Elsevier Inc. |
| Keywords: | human cell; nonhuman; adenocarcinoma; cell proliferation; mouse; phenotype; animal experiment; animal model; lung cancer; cell differentiation; tumor xenograft; drug resistance; hyperplasia; transcriptome; endoderm; differentiation; tumor progression; plasticity; epithelial mesenchymal transition; tumor heterogeneity; cell plasticity; human; priority journal; article; chromatin state; tumor evolution; genetically engineered mouse strain; single-cell transcriptomics; cell state transition |
| Journal Title: | Cancer Cell |
| Volume: | 38 |
| Issue: | 2 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2020-08-10 |
| Start Page: | 229 |
| End Page: | 246.e13 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2020.06.012 |
| PUBMED: | 32707077 |
| PROVIDER: | scopus |
| PMCID: | PMC7745838 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2020 -- Source: Scopus |
