دورية أكاديمية
Epigenetic Regulators Open the Door to SCLC Plasticity.
| العنوان: | Epigenetic Regulators Open the Door to SCLC Plasticity. |
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| المؤلفون: | Weber MC; Department of Pharmacology & Cancer Biology, Duke University, Durham, North Carolina., Izzo LT; Department of Pharmacology & Cancer Biology, Duke University, Durham, North Carolina., Oliver TG; Department of Pharmacology & Cancer Biology, Duke University, Durham, North Carolina. |
| المصدر: | Cancer research [Cancer Res] 2023 Nov 01; Vol. 83 (21), pp. 3495-3497. |
| نوع المنشور: | Journal Article; Comment |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Lung Neoplasms*/pathology , Small Cell Lung Carcinoma*/pathology, Animals ; Mice ; Cell Line, Tumor ; Histone Demethylases/metabolism ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic |
| مستخلص: | Small-cell lung cancer (SCLC) is a neuroendocrine tumor type with limited treatment options and poor prognosis. SCLC comprises multiple molecular subtypes that are defined by the expression of the lineage-related transcription factors ASCL1, NEUROD1, POU2F3, and more controversially, YAP1. SCLC exhibits remarkable plasticity with the capacity to transition between molecular states; because these states are associated with unique therapeutic susceptibilities, SCLC has been likened to a moving therapeutic target. While MYC's role in driving the ASCL1-to-NEUROD1 (A-to-N) transition is established, additional mechanisms governing SCLC plasticity remain largely obscure. A recent study by Duplaquet and colleagues, published in Nature Cell Biology, employs an innovative genetically engineered mouse model of SCLC harboring loss of KDM6A-a histone lysine demethylase mutated in approximately 2% of SCLC cases. KDM6A loss in SCLC alters chromatin accessibility and increases the potential for A-to-N plasticity in vivo. Through characterization of the epigenetic landscape, Duplaquet and colleagues identified histone methylation as a key regulator of SCLC plasticity. These findings provide not only a new model system for studying SCLC plasticity, but also identify new epigenetic mechanisms involved, which will ultimately be critical for designing more effective therapies. (©2023 American Association for Cancer Research.) |
| التعليقات: | Comment on: Nat Cell Biol. 2023 Sep;25(9):1346-1358. doi: 10.1038/s41556-023-01210-z. (PMID: 37591951) |
| معلومات مُعتمدة: | T32 GM007171 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | EC 1.14.11.- (Histone Demethylases) |
| تواريخ الأحداث: | Date Created: 20230927 Date Completed: 20231102 Latest Revision: 20240719 |
| رمز التحديث: | 20240719 |
| DOI: | 10.1158/0008-5472.CAN-23-2922 |
| PMID: | 37756567 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
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| DOI: | 10.1158/0008-5472.CAN-23-2922 |