ArticleCancer cell2020
Emergence of a High-Plasticity Cell State during Lung Cancer Evolution.
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Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 264 papers.
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0cells of the map it votes in
264citing papers in PubMed
17.6field-weighted citation impact, top 1% of its field
What it found
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Who cites it
264 citing papers in PubMed, 384 citations in OpenAlex.
- Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026Review
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency.Science advances · 2026Article
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance.Nature genetics · 2026Article
- STEAP2 Is a Candidate Marker of a 7q/CNA-Associated Iron-Handling Malignant Epithelial State in Lung Adenocarcinoma.Cancers · 2026Article
- Joint inference of paired dynamical gene regulatory networks reveals distinct cell-state landscapes of neutrophil reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis.Nature genetics · 2026Article
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- 3'UTR-directed, kinase-proximal mRNA decay inhibits C/EBPβ phosphorylation/activation to suppress senescence in tumor cells.iScience · 2026Article
- The Metabolic Rheostat Index Uncovers Pathway-Level Coordination, Immunosuppressive Microenvironment Remodeling, and Therapeutic Co-Vulnerabilities in Pancreatic Ductal Adenocarcinoma.Current issues in molecular biology · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- An early invasive signature from the adenocarcinoma in situ-to-invasive adenocarcinoma single-cell trajectory stratifies stage I lung adenocarcinoma overall survival.Journal of thoracic disease · 2026Article
- Deciphering lung cancer at high resolution: a narrative review of applications of single-cell and spatial transcriptomics sequencing.Translational lung cancer research · 2026Review
- PRKCI-ECT2 copy number gain promotes developmental reprogramming and metastatic competence in lung adenocarcinoma.Cell reports · 2026Article
- Multiple distinct metastatic cell states are induced by epithelial-mesenchymal plasticity.bioRxiv : the preprint server for biology · 2026Article
- Integrated stress response couples mitochondrial fitness with lineage reprogramming to drive cancer evolution.Nature cell biology · 2026Article
- Targeting thymine DNA glycosylase induces synthetic lethality in p53-deficient cancers.Nature chemical biology · 2026Article
- HNF4α controls growth, identity, and KRAS inhibitor response in invasive mucinous adenocarcinoma of the lung.The Journal of clinical investigation · 2026Article
- Transitional cell states at the crossroads of development, disease, and repair-regeneration.Physiological reviews · 2026Review
204 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors at 6 institutions in 2 countries.
Nemanja Despot MarjanovicKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Computational and Systems Biology PhD Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Matan HofreeKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jason E ChanCancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
David CannerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Katherine WuCancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Marianna TrakalaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Griffin G HartmannCancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Olivia C SmithKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Jonathan Y KimKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Kelly Victoria EvansWellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
Anna HudsonCancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Orr AshenbergKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Caroline B M PorterKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alborz BejnoodKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ayshwarya SubramanianKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kenneth PitterCancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Yan YanCancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Toni DeloreyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Devan R PhillipsKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nisargbhai ShahDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ojasvi ChaudharyThe Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Alexander TsankovKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Travis HollmannDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Natasha RekhtmanDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Pierre P MassionDepartment of Medicine and Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
John T PoirierDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Linas MazutisThe Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ruifang LiEpigenetics Technology Innovation Lab, Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Joo-Hyeon LeeWellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
Angelika AmonDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Tyler JacksDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: tjacks@mit.edu.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: aregev@broadinstitute.org.
Tuomas TammelaCancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Cell and Developmental Biology, Weill-Cornell Medical College, New York, NY 10065, USA. Electronic address: tammelat@mskcc.org.
Memorial Sloan Kettering Cancer Center · USBroad Institute · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · USWellcome/MRC Cambridge Stem Cell Institute · GBVanderbilt University Medical Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MVirology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5MVIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9MUSE OF RETROVIRUS PROMOTER TRAP VECTORS TO IDENTIFY ONCOGENES AND ANTI-ONCOGENESP01CA042063 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI JACKS, TYLER E. · 1986 to 2021
$30.5MInvestigational Cancer Therapeutics Training Program (ICTTP)T32CA009207 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Omar Abdel-Wahab, Alexander Drilon · 1985 to 2026
$13.7MCellular, molecular and quantitative imaging analysis of screening-detected lung adenocarcinomaU01CA196405 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MALDONADO, FABIEN · 2015 to 2020
$5.4MInvestigating cellular heterogeneity in lung cancerR00CA187317 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI TAMMELA, TUOMAS · 2017 to 2019
$757kInvestigating Wnt and Lgr5 signaling as regulators of lung cancer heterogeneityK99CA187317 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TAMMELA, TUOMAS · 2014 to 2015
$246kHoward Hughes Medical InstituteMedical Research Council MC_PC_12009Medical Research Council MC_PC_17230NCI NIH HHS K99 CA187317NCI NIH HHS P01 CA042063NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014051NCI NIH HHS R00 CA187317NCI NIH HHS T32 CA009207NCI NIH HHS U01 CA196405
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.
Indexed as
AnimalsCell DifferentiationCell Line, TumorCell PlasticityCell ProliferationCells, CulturedDisease Models, AnimalEpithelial CellsEpithelial-Mesenchymal TransitionGenetic HeterogeneityHumansLung NeoplasmsMiceNeoplastic Stem CellsSingle-Cell AnalysisTranscriptomecell state transitionchromatin statedifferentiationdrug resistancelung cancerplasticitysingle-cell transcriptomicstumor evolutiontumor heterogeneitytumor progression
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