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TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer.
Nat Commun
July 2024
School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, 637551, Singapore.
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.
View Article and Find Full Text PDFTrigonelline is an NAD precursor that improves muscle function during ageing and is reduced in human sarcopenia.
Nat Metab
March 2024
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
Article Synopsis
- Mitochondrial dysfunction and low NAD levels are linked to aging and muscle loss (sarcopenia), but it's unclear if these issues come from local or systemic factors.
- Research shows that trigonelline, a natural compound similar to nicotinic acid, positively affects NAD levels and muscle health across different species, including humans.
- Trigonelline enhances mitochondrial function, reduces muscle wasting, and increases strength and lifespan, suggesting that dietary trigonelline could be a helpful strategy against age-related muscle decline.
Bioinformatics analysis of MMP14+ myeloid cells affecting endothelial-mesenchymal transformation and immune microenvironment in glioma.
Heliyon
March 2024
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China.
Background: Gliomas, known for their complex and aggressive characteristics, are deeply influenced by the tumor microenvironment. Matrix metalloproteinases (MMPs) play a vital role in shaping this environment, presenting an opportunity for novel treatment strategies.
Methods: We collected six bulk RNA datasets, one single-cell RNA sequencing (scRNA-seq) dataset, and gene sets related to Matrix Metalloproteinases (MMPs), Endothelial-Mesenchymal Transformation (EndMT), and sprouting angiogenesis.
A molecular circuit linking the BCR to the NAD biosynthetic enzyme NAMPT is an actionable target in Richter syndrome.
Blood Adv
April 2024
Laboratory of Functional Genomics, Department of Medical Sciences, University of Turin, Turin, Italy.
This works defines, to the best of our knowledge, for the first time a molecular circuit connecting nicotinamide mononucleoside phosphoribosyl transferase (NAMPT) activity to the B-cell receptor (BCR) pathway. Using 4 distinct xenograft models derived from patients with Richter syndrome (RS-PDX), we show that BCR cross-linking results in transcriptional activation of the nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme NAMPT, with increased protein expression, in turn, positively affecting global cellular NAD levels and sirtuins activity. NAMPT blockade, by using the novel OT-82 inhibitor in combination with either BTK or PI3K inhibitors (BTKi or PI3Ki), induces rapid and potent apoptotic responses in all 4 models, independently of their mutational profile and the expression of the other NAD biosynthetic enzymes, including nicotinate phosphoribosyltransferase.
View Article and Find Full Text PDFAssessment of serum and salivary visfatin levels in newly diagnosed patients of type-II DM.
J Oral Maxillofac Pathol
December 2023
Department of Oral and Maxillofacial Pathology and Oral Microbiology, Narayana Dental College, and Hospital, Chinthareddypalem, Nellore, Andhra Pradesh, India.
Background: Type II diabetes mellitus (T2DM) is a metabolic disorder. It is thought to be an autoinflammatory disease, as inflammatory mediators are associated with the progression of the disease. Visfatin, an adipokine, is linked to insulin resistance.
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