دورية أكاديمية
أعرض في EDS

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment.

التفاصيل البيبلوغرافية
العنوان: Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment.
المؤلفون: Guerrero-Juarez CF; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA.; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA.; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA., Lee GH; Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA., Liu Y; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA., Wang S; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA.; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA., Karikomi M; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA., Sha Y; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA., Chow RY; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Nguyen TTL; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Iglesias VS; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Aasi S; Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA., Drummond ML; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Nie Q; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.; Department of Mathematics, University of California, Irvine, Irvine, CA 92697, USA.; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA.; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA., Sarin K; Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA., Atwood SX; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, Irvine, CA 92697, USA.; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.; Department of Dermatology, University of California, Irvine, Irvine, CA 92697, USA.; Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA.
المصدر: Science advances [Sci Adv] 2022 Jun 10; Vol. 8 (23), pp. eabm7981. Date of Electronic Publication: 2022 Jun 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
مواضيع طبية MeSH: Carcinoma, Basal Cell*/drug therapy , Carcinoma, Basal Cell*/genetics , Carcinoma, Basal Cell*/metabolism , Skin Neoplasms*/genetics , Skin Neoplasms*/pathology, Animals ; Ecosystem ; Hedgehog Proteins ; Humans ; Mice ; Single-Cell Analysis ; Tumor Microenvironment
مستخلص: How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity-PAGA, cellular entropy, and regulon analysis in stromal cells reveals a cancer-specific rewiring of fibroblasts, where STAT1, TGF-β, and inflammatory signals induce a noncanonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, whose expression we validated in situ. Last, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro vismodegib-resistant BCC cell growth, Hedgehog signaling, and in vivo tumor growth in a BCC mouse model, validating HSP70's essential role in tumor growth and reinforcing the critical nature of tumor microenvironment cross-talk in BCC progression.
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معلومات مُعتمدة: R01 CA237563 United States CA NCI NIH HHS; P30 AR075047 United States AR NIAMS NIH HHS; R01 GM123731 United States GM NIGMS NIH HHS; P30 CA062203 United States CA NCI NIH HHS; K23 CA211793 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Hedgehog Proteins)
تواريخ الأحداث: Date Created: 20220610 Date Completed: 20220614 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC9187229
DOI: 10.1126/sciadv.abm7981
PMID: 35687691
قاعدة البيانات: MEDLINE
الوصف
تدمد:2375-2548
DOI:10.1126/sciadv.abm7981