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Carcinoma-associated fibroblasts (CAFs) consist of heterogeneous subpopulations that play a critical role in the dynamics of the tumor microenvironment. The extracellular signals of CAFs have been attributed to the extracellular matrix, cytokines, cell surface checkpoints, and exosomes. In the present study, it is demonstrated that the CD10 transmembrane hydrolase expressed on a subset of CAFs supports tumor stemness and induces chemoresistance. Mechanistically, CD10 degenerates an antitumoral peptide termed osteogenic growth peptide (OGP). OGP restrains the expression of rate-limiting desaturase SCD1 and inhibits lipid desaturation, which is required for cancer stem cells (CSCs). Targeting CD10 significantly improves the efficacy of chemotherapy in vivo. Clinically, CD10-OGP signals are associated with the response to neoadjuvant chemotherapy in patients with breast cancer. The collective data suggest that a nexus between the niche and lipid metabolism in CSCs is a promising therapeutic target for breast cancer.
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http://dx.doi.org/10.1002/advs.202101848 | DOI Listing |
Haematologica
September 2025
Center for Cardiometabolic Science, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky,.
Maintaining a healthy pool of circulating red blood cells (RBCs) is essential for adequate perfusion, as even minor changes in the population can impair oxygen delivery, resulting in serious health complications including tissue ischemia and organ dysfunction. This responsibility largely falls to specialized macrophages in the spleen, known as red pulp macrophages, which efficiently take up and recycle damaged RBCs. However, questions remain regarding how these macrophages are acutely activated to accommodate increased demand.
View Article and Find Full Text PDFVasc Specialist Int
September 2025
Department of Vascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
An abdominal aortic aneurysm (AAA) is defined as a localized dilation of the abdominal aorta measuring at least 1.5 times its normal diameter. If left untreated, AAA can progress to a life-threatening condition.
View Article and Find Full Text PDFCell Death Differ
September 2025
Graduate Institute of Physiology, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan, Republic of China.
Peroxisome proliferator-activated receptor alpha (PPARα) is a crucial transcriptional factor that regulates fatty acid β-oxidation and ketogenesis in response to fasting. However, the mechanisms underlying PPARα function remain unclear. This study identified a novel PPARα-binding protein-RING finger protein 128 (RNF128)-that facilitates PPARα polyubiquitination, resulting in the degradation and suppression of PPARα function during fasting.
View Article and Find Full Text PDFNature
September 2025
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFOncogene
September 2025
Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, China.