Search Results (3)

Increasing recognition of the importance of the tumor microenvironment (TME) in cancer therapeutic strategies has led to more efforts to target molecules in the TME. Vasorin (VASN) is a transmembrane glycoprotein that can be cleaved and released into the extracellular matrix in a soluble form (sVASN), which is regarded as a decoy that inhibits the TGF-β signaling pathway. VASN is upregulated under hypoxic or tumorigenic conditions to regulate tumor progression. In this study, cell surface CD71 was identified as a specific binding protein of sVASN and mediated the internalization of sVASN in cancerous, endothelial and T cells. Endocytosed sVASN enhanced the nuclear translocation of p-STAT3(Tyr705), leading to the activation of a cascade of genes, ultimately contributing to tumor malignant progression. In cancer cells, sVASN promoted cell proliferation and migration by upregulating the YAP1/TAZ or mTOR-AKT pathways and it promotes stemness maintenance by regulating Notch1. In endothelial cells, sVASN facilitated angiogenesis through the VEGF signaling pathway. In T cells, sVASN inhibited the activation of T cells through AKT pathway. This study elucidated the mechanism by which sVASN acts as a tumor-promoting factor to accelerate tumor malignant progression through cell-surface CD71 and presented sVASN as a novel target for cancer therapy. Full article

Vasorin (VASN), a transmembrane protein heavily expressed in endothelial cells, has garnered recent interest due to its key role in vascular development and pathology. The oligomeric state of VASN is a crucial piece of knowledge given that receptor clustering is a frequent regulatory mechanism in downstream signaling activation and amplification. However, documentation of VASN oligomerization is currently absent. In this brief report, we describe the measurement of VASN oligomerization in its native membranous environment, leveraging a class of fluorescence fluctuation spectroscopy. Our investigation revealed that the majority of VASN resides in a monomeric state, while a minority of VASN forms homodimers in the cellular membrane. This result raises the intriguing possibility that ligand-independent clustering of VASN may play a role in transforming growth factor signaling. Full article

Abnormal vasorin (Vasn) expression occurs in multiple diseases, particularly liver cancers. Vasn knockout (KO) in mice causes malnutrition, a shortened life span, and decreased physiological functions. However, the causes and underlying mechanisms remain unknown. Here, we established Vasn KO C57BL/6J mice by using the CRISPR/Cas9 system. The animals were weighed, and histology, immunohistochemistry, electronic microscopy, and liver function tests were used to examine any change in the livers. Autophagy markers were detected by Western blotting. MicroRNA (miRNA) sequencing was performed on liver samples and analyses to study the signaling pathway altered by Vasn KO. Significant reductions in mice body and liver weight, accompanied by abnormal liver function, liver injury, and reduced glycogen accumulation in hepatocytes, were observed in the Vasn KO mice. The deficiency of Vasn also significantly increased the number of autophagosomes and the expression of LC3A/B-II/I but decreased SQSTM1/p62 levels in hepatocytes, suggesting aberrant activation of autophagy. Vasn deficiency inhibited glycogen-mediated mammalian target of rapamycin (mTOR) phosphorylation and activated Unc-51-like kinase 1 (ULK1) signaling, suggesting that Vasn deletion upregulates hepatocyte autophagy through the mTOR-ULK1 signaling pathway as a possible cause of diminished life span and health. Our results indicate that Vasn is required for the homeostasis of liver glycogen metabolism upstream of hepatocyte autophagy, suggesting research values for regulating Vasn in pathways related to liver physiology and functions. Overall, this study provides new insight into the role of Vasn in liver functionality. Full article