Secreted Frizzled Related Proteins (Sfrps) are a family of secreted proteins that can bind both to Wnt ligands and Frizzled receptors, thereby modulating the Wnt signalling cascades. Recent studies have shown that Sfrps can also interact with Wnt unrelated molecules such as RANKL, a member of the tumor necrosis factor family, Tolloid metalloproteinases or integrin-fibronectin complexes. Alterations in the levels of Sfrp expression have been recently associated with different pathological conditions, including tumor formation and bone and myocardial disorders. Here, we summarise the evidence that relates Sfrps with these diseases and discuss how the proposed multiple Sfrp interactions with Wnt related and unrelated pathways may explain their implication in such diverse pathologies.
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http://dx.doi.org/10.1620/tjem.221.11 | DOI Listing |
Curr Drug Targets
January 2025
Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL33458, United States.
Diseases affecting bone encompass a spectrum of disorders, from prevalent conditions such as osteoporosis and Paget's disease, collectively impacting millions, to rare genetic disorders including Fibrodysplasia Ossificans Progressiva (FOP). While several classes of drugs, such as bisphosphonates, synthetic hormones, and antibodies, are utilized in the treatment of bone diseases, their efficacy is often curtailed by issues of tolerability and high incidence of adverse effects. Developing therapeutic agents for bone diseases is hampered by the fact that numerous pathways regulating bone metabolism also perform pivotal functions in other organ systems.
View Article and Find Full Text PDFSci Adv
December 2024
Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada.
Wnt proteins are hydrophobic glycoproteins that are nevertheless capable of long-range signaling. We found that Wnt7a is secreted long distance on the surface of extracellular vesicles (EVs) following muscle injury. We defined a signal peptide region in Wnts required for secretion on EVs, termed exosome-binding peptide (EBP).
View Article and Find Full Text PDFEBioMedicine
October 2024
IRCM, Montpellier Cancer Research Institute, INSERM U1194, Montpellier University, Montpellier, F-34298, France; ICM, Institut Régional du Cancer de Montpellier, Montpellier, F-34298, France. Electronic address:
Background: We studied the poorly-known dynamics of circulating DNA (cir-nDNA), as monitored prospectively over an extended post-surgery period, in patients with cancer.
Methods: On patients with stage III colon cancer (N = 120), using personalised molecular tags we carried out the prospective, multicenter, blinded cohort study of the post-surgery serial analysis of cir-nDNA concentration. 74 patients were included and 357 plasma samples tested.
Nat Cell Biol
August 2024
Department of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Circular RNA (circRNA) is covalently closed, single-stranded RNA produced by back-splicing. A few circRNAs have been implicated as functional; however, we lack understanding of pathways that are regulated by circRNAs. Here we generated a pooled short-hairpin RNA library targeting the back-splice junction of 3,354 human circRNAs that are expressed at different levels (ranging from low to high) in humans.
View Article and Find Full Text PDFCells
July 2024
IIAIGC Study Center, Burlington, VT 05408, USA.
Lorlatinib is a pharmaceutical ALK kinase inhibitor used to treat ALK driven non-small cell lung cancers. This paper analyses the intersection of past published data on the physiological consequences of two unrelated drugs from general medical practice-itraconazole and cilostazol-with the pathophysiology of ALK positive non-small cell lung cancer. A conclusion from that data analysis is that adding itraconazole and cilostazol may make lorlatinib more effective.
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