دورية أكاديمية
أعرض في EDS

Archetype tasks link intratumoral heterogeneity to plasticity and cancer hallmarks in small cell lung cancer.

التفاصيل البيبلوغرافية
العنوان: Archetype tasks link intratumoral heterogeneity to plasticity and cancer hallmarks in small cell lung cancer.
المؤلفون: Groves SM; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA., Ildefonso GV; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA., McAtee CO; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA., Ozawa PMM; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA., Ireland AS; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Stauffer PE; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA., Wasdin PT; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA., Huang X; Utah Center for Genetic Discovery, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Qiao Y; Utah Center for Genetic Discovery, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Lim JS; Department of Pediatrics and Genetics, Stanford University, Stanford, CA 94305, USA., Bader J; Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Liu Q; Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37235, USA., Simmons AJ; Epithelial Biology Center and Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37235, USA., Lau KS; Epithelial Biology Center and Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37235, USA., Iams WT; Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37235, USA., Hardin DP; Department of Mathematics and Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37235, USA., Saff EB; Department of Mathematics, Vanderbilt University, Nashville, TN 37235, USA., Holmes WR; Department of Mathematics, Vanderbilt University, Nashville, TN 37235, USA; Department of Physics, Vanderbilt University, Nashville, TN 37235, USA., Tyson DR; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA., Lovly CM; Department of Mathematics and Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37235, USA., Rathmell JC; Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Marth G; Utah Center for Genetic Discovery, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Sage J; Department of Pediatrics and Genetics, Stanford University, Stanford, CA 94305, USA., Oliver TG; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Weaver AM; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37235, USA., Quaranta V; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA. Electronic address: vito.quaranta@vanderbilt.edu.
المصدر: Cell systems [Cell Syst] 2022 Sep 21; Vol. 13 (9), pp. 690-710.e17. Date of Electronic Publication: 2022 Aug 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101656080 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2405-4720 (Electronic) Linking ISSN: 24054712 NLM ISO Abbreviation: Cell Syst Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2015]-
مواضيع طبية MeSH: Lung Neoplasms*/genetics , Lung Neoplasms*/pathology , Small Cell Lung Carcinoma*/genetics , Small Cell Lung Carcinoma*/metabolism , Small Cell Lung Carcinoma*/pathology, Cell Plasticity ; Humans
مستخلص: Small cell lung cancer (SCLC) tumors comprise heterogeneous mixtures of cell states, categorized into neuroendocrine (NE) and non-neuroendocrine (non-NE) transcriptional subtypes. NE to non-NE state transitions, fueled by plasticity, likely underlie adaptability to treatment and dismal survival rates. Here, we apply an archetypal analysis to model plasticity by recasting SCLC phenotypic heterogeneity through multi-task evolutionary theory. Cell line and tumor transcriptomics data fit well in a five-dimensional convex polytope whose vertices optimize tasks reminiscent of pulmonary NE cells, the SCLC normal counterparts. These tasks, supported by knowledge and experimental data, include proliferation, slithering, metabolism, secretion, and injury repair, reflecting cancer hallmarks. SCLC subtypes, either at the population or single-cell level, can be positioned in archetypal space by bulk or single-cell transcriptomics, respectively, and characterized as task specialists or multi-task generalists by the distance from archetype vertex signatures. In the archetype space, modeling single-cell plasticity as a Markovian process along an underlying state manifold indicates that task trade-offs, in response to microenvironmental perturbations or treatment, may drive cell plasticity. Stifling phenotypic transitions and plasticity may provide new targets for much-needed translational advances in SCLC. A record of this paper's Transparent Peer Review process is included in the supplemental information.
Competing Interests: Declaration of interests C.M.L. is a consultant/advisory board member for Pfizer, Novartis, Astra Zeneca, Genoptix, Sequenom, Ariad, Takeda, Blueprints Medicine, Cepheid, Foundation Medicine, Roche, Achilles Therapeutics, Genentech, Syros, Amgen, EMD Serono, and Eli Lilly and reports receiving commercial research grants from Xcovery, Astra Zeneca, and Novartis. W.T.I. is a consultant/advisory board member for Genentech, Jazz Pharma, G1 Therapeutics, Mirati, OncLive, Clinical Care Options, Chardan, Outcomes Insights, Cello Health, and Curio Science. T.G.O. is a consultant/advisory board member for Known Medicine. J.S. receives research funding from Pfizer. V.Q. is an Academic co-Founder and equity holder for Parthenon Therapeutics, Inc. and Duet BioSystems, Inc.
(Copyright © 2022. Published by Elsevier Inc.)
التعليقات: Comment in: Cell Syst. 2022 Sep 21;13(9):687-689. (PMID: 36137510)
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معلومات مُعتمدة: U01 CA224276 United States CA NCI NIH HHS; U24 CA213274 United States CA NCI NIH HHS; K12 CA090625 United States CA NCI NIH HHS; R01 DK106228 United States DK NIDDK NIH HHS; U01 CA231844 United States CA NCI NIH HHS; R50 CA243783 United States CA NCI NIH HHS; UG1 CA233259 United States CA NCI NIH HHS; P50 CA236733 United States CA NCI NIH HHS; U01 CA215845 United States CA NCI NIH HHS; R01 CA251147 United States CA NCI NIH HHS; U01 CA215798 United States CA NCI NIH HHS; U54 CA217450 United States CA NCI NIH HHS; K00 CA234920 United States CA NCI NIH HHS; R01 CA217987 United States CA NCI NIH HHS; R01 DK103831 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: RNA velocity; dynamical systems; gene regulatory networks; heterogeneity; phenotypic plasticity; single cell; small cell lung cancer
تواريخ الأحداث: Date Created: 20220818 Date Completed: 20220926 Latest Revision: 20240213
رمز التحديث: 20240213
مُعرف محوري في PubMed: PMC9615940
DOI: 10.1016/j.cels.2022.07.006
PMID: 35981544
قاعدة البيانات: MEDLINE
الوصف
تدمد:2405-4720
DOI:10.1016/j.cels.2022.07.006