دورية أكاديمية
MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate.
| العنوان: | MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate. |
|---|---|
| المؤلفون: | Ireland AS; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Micinski AM; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Kastner DW; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Guo B; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Wait SJ; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Spainhower KB; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Conley CC; Huntsman Cancer Institute Bioinformatic Analysis Shared Resource, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Chen OS; Huntsman Cancer Institute High-Throughput Genomics Shared Resource, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Guthrie MR; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Soltero D; Department of Oncological Sciences, Huntsman Cancer Institute, 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., Huang X; Utah Center for Genetic Discovery, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Tarapcsák S; Utah Center for Genetic Discovery, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Devarakonda S; Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Chalishazar MD; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Gertz J; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Moser JC; HonorHealth Research Institute, Scottsdale, AZ 85254, USA., Marth G; Utah Center for Genetic Discovery, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA., Puri S; Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA., Witt BL; Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA; ARUP Laboratories at University of Utah, Salt Lake City, UT 84108, USA., Spike BT; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA., Oliver TG; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: trudy.oliver@hci.utah.edu. |
| المصدر: | Cancer cell [Cancer Cell] 2020 Jul 13; Vol. 38 (1), pp. 60-78.e12. Date of Electronic Publication: 2020 May 30. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Gene Expression Regulation, Neoplastic*, Lung Neoplasms/*genetics , Neuroendocrine Tumors/*genetics , Proto-Oncogene Proteins c-myc/*genetics , Small Cell Lung Carcinoma/*genetics, Animals ; Cell Line, Tumor ; Disease Models, Animal ; Gene Expression Profiling/methods ; Genetic Heterogeneity ; Humans ; Lung Neoplasms/metabolism ; Mice, Knockout ; Neuroendocrine Tumors/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction/genetics ; Single-Cell Analysis ; Small Cell Lung Carcinoma/metabolism |
| مستخلص: | Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1, NEUROD1, POU2F3, or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes. In neuroendocrine cells, MYC activates Notch to dedifferentiate tumor cells, promoting a temporal shift in SCLC from ASCL1 + to NEUROD1 + to YAP1 + states. MYC alternatively promotes POU2F3 + tumors from a distinct cell type. Human SCLC exhibits intratumoral subtype heterogeneity, suggesting that this dynamic evolution occurs in patient tumors. These findings suggest that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype. Competing Interests: Declaration of Interests T.G.O. has pending patent applications related to subtype stratification of SCLC: US16/335368, JP2019522392, and EP2017865057. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cancer Cell. 2020 Jul 13;38(1):17-20. (PMID: 32663464) |
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| معلومات مُعتمدة: | P30 CA042014 United States CA NCI NIH HHS; R21 CA216504 United States CA NCI NIH HHS; U01 CA231844 United States CA NCI NIH HHS; U24 CA213274 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: ASCL1; MYC; NEUROD1; NOTCH; SCLC; YAP1; mouse models; neuroendocrine; plasticity; tumor evolution |
| المشرفين على المادة: | 0 (MYC protein, human) 0 (Proto-Oncogene Proteins c-myc) 0 (Receptors, Notch) |
| تواريخ الأحداث: | Date Created: 20200601 Date Completed: 20210308 Latest Revision: 20240206 |
| رمز التحديث: | 20240206 |
| مُعرف محوري في PubMed: | PMC7393942 |
| DOI: | 10.1016/j.ccell.2020.05.001 |
| PMID: | 32473656 |
| قاعدة البيانات: | MEDLINE |
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