دورية أكاديمية
أعرض في EDS

TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer.

التفاصيل البيبلوغرافية
العنوان: TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer.
المؤلفون: Sim N; School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, 637551, Singapore., Carter JM; School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, 637551, Singapore., Deka K; School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, 637551, Singapore., Tan BKT; Division of Surgery and Surgical Oncology, Department of Breast Surgery, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore, 168583, Singapore.; Division of Surgery and Surgical Oncology, Department of Breast Surgery, Singapore General Hospital, 31 Third Hospital Ave, Singapore, 168753, Singapore.; SingHealth Duke-NUS Breast Centre, Singapore, Singapore., Sim Y; Division of Surgery and Surgical Oncology, Department of Breast Surgery, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore, 168583, Singapore.; Division of Surgery and Surgical Oncology, Department of Breast Surgery, Singapore General Hospital, 31 Third Hospital Ave, Singapore, 168753, Singapore.; SingHealth Duke-NUS Breast Centre, Singapore, Singapore., Tan SM; School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, 637551, Singapore., Li Y; School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, 637551, Singapore. liyh@ntu.edu.sg.
المصدر: Nature communications [Nat Commun] 2024 Jul 05; Vol. 15 (1), pp. 5638. Date of Electronic Publication: 2024 Jul 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Triple Negative Breast Neoplasms*/metabolism , Triple Negative Breast Neoplasms*/genetics , Triple Negative Breast Neoplasms*/pathology , TWEAK Receptor*/metabolism , TWEAK Receptor*/genetics , Cytokine TWEAK*/metabolism , Cytokine TWEAK*/genetics , Signal Transduction* , Nicotinamide Phosphoribosyltransferase*/metabolism , Nicotinamide Phosphoribosyltransferase*/genetics , Gene Expression Regulation, Neoplastic*, Humans ; Female ; Animals ; Cell Line, Tumor ; Mice ; Neoplasm Metastasis ; Cytokines/metabolism ; Enhancer Elements, Genetic/genetics
مستخلص: Triple Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype suffering from limited targeted treatment options. Following recent reports correlating Fibroblast growth factor-inducible 14 (Fn14) receptor overexpression in Estrogen Receptor (ER)-negative breast cancers with metastatic events, we show that Fn14 is specifically overexpressed in TNBC patients and associated with poor survival. We demonstrate that constitutive Fn14 signalling rewires the transcriptomic and epigenomic landscape of TNBC, leading to enhanced tumour growth and metastasis. We further illustrate that such mechanisms activate TNBC-specific super enhancers (SE) to drive the transcriptional activation of cancer dependency genes via chromatin looping. In particular, we uncover the SE-driven upregulation of Nicotinamide phosphoribosyltransferase (NAMPT), which promotes NAD+ and ATP metabolic reprogramming critical for filopodia formation and metastasis. Collectively, our study details the complex mechanistic link between TWEAK/Fn14 signalling and TNBC metastasis, which reveals several vulnerabilities which could be pursued for the targeted treatment of TNBC patients.
(© 2024. The Author(s).)
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معلومات مُعتمدة: NRF-NRFF2018-04 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore); NAP-SUG Nanyang Technological University (NTU)
المشرفين على المادة: 0 (TWEAK Receptor)
0 (Cytokine TWEAK)
0 (TNFRSF12A protein, human)
EC 2.4.2.12 (Nicotinamide Phosphoribosyltransferase)
EC 2.4.2.12 (nicotinamide phosphoribosyltransferase, human)
0 (Cytokines)
0 (TNFSF12 protein, human)
تواريخ الأحداث: Date Created: 20240704 Date Completed: 20240704 Latest Revision: 20240707
رمز التحديث: 20240707
مُعرف محوري في PubMed: PMC11224303
DOI: 10.1038/s41467-024-50071-z
PMID: 38965263
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-024-50071-z