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Publication : Emergence of a High-Plasticity Cell State during Lung Cancer Evolution.

First Author  Marjanovic ND Year  2020
Journal  Cancer Cell Volume  38
Issue  2 Pages  229-246.e13
PubMed ID  32707077 Mgi Jnum  J:296323
Mgi Id  MGI:6466880 Doi  10.1016/j.ccell.2020.06.012
Citation  Marjanovic ND, et al. (2020) Emergence of a High-Plasticity Cell State during Lung Cancer Evolution. Cancer Cell 38(2):229-246.e13
abstractText  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.
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