The Multifunctional Protein Syntenin-1: Regulator of Exosome Biogenesis, Cellular Function, and Tumor Progression.

Syntenin acts as an adaptor and scaffold protein through its two PSD-95, Dlg, and ZO-1 (PDZ) domains, participating in multiple signaling pathways and modulating cellular physiology. It has been identified as an oncogene, promoting cancer development, metastasis, and angiogenesis in various carcinomas. Syntenin-1 is also associated with the production and release of exosomes, small extracellular vesicles that play a significant role in intercellular communication by containing bioactive molecules such as proteins, lipids, and nucleic acids. The trafficking of exosomes involves a complex interplay of various regulatory proteins, including syntenin-1, which interacts with its binding partners, syndecan and activated leukocyte cell adhesion molecule (ALIX). Exosomal transfer of microRNAs, a key cargo, can regulate the expression of various cancer-related genes, including syntenin-1. Targeting the mechanism involving the regulation of exosomes by syntenin-1 and microRNAs may provide a novel treatment strategy for cancer. This review highlights the current understanding of syntenin-1's role in regulating exosome trafficking and its associated cellular signaling pathways.

Checkpoint Kinase 1 (CHK1) Functions as Both a Diagnostic Marker and a Regulator of Epithelial-to-Mesenchymal Transition (EMT) in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is more difficult to treat and has a higher mortality rate than other subtypes. Although hormone receptor-targeted therapy is an effective treatment to increase survival rate in breast cancer patients, it is not suitable for TNBC patients. To address the issues, differentially expressed genes (DEGs) in TNBC patients from the Gene Expression Omnibus (GEO) database were analyzed. A total of 170 genes were obtained from three Genomic Spatial Events (GSEs) using the intersection of each GSE dataset and 61 DEGs were identified after validation with the gene enrichment analysis. We combined this with the degree scores from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network, of which 7 genes were correlated with survival rate. Finally, a proteomics database revealed that only the CHK1 protein level was differently expressed in basal-like compared with other subtypes. We demonstrated that CHK1 expression was higher in TNBC cell lines compared with non-TNBC cell lines, and CHK1 promotes epithelial to mesenchymal transition (EMT) as well as migration and invasion ability. Our study provides new insight into the TNBC subnetwork that may be useful in the prognosis and treatment of TNBC patients.

Functional Characterization of Endothelial Cells Differentiated from Porcine Epiblast Stem Cells.

Endothelial cells (ECs), lining blood vessels' lumen, play an essential role in regulating vascular functions. As multifunctional components of vascular structures, pluripotent stem cells (PSCs) are the promising source for potential therapeutic applications in various vascular diseases. Our laboratory has previously established an approach for differentiating porcine epiblast stem cells (pEpiSCs) into ECs, representing an alternative and potentially superior cell source. However, the condition of pEpiSCs-derived ECs growth has yet to be determined, and whether pEpiSCs differentiate into functional ECs remained unclear. Changes in morphology, proliferation and functional endothelial marker were assessed in pEpiSCs-derived ECs in vitro. pEpiSCs-derived ECs were subjected to magnetic-activated cell sorting (MACS) to collect CD-31+ of ECs. We found that sorted ECs showed the highest proliferation rate in differentiation media in primary culture and M199 media in the subculture. Next, sorted ECs were examined for their ability to act as typical vascular ECs through capillary-like structure formation assay, Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake, and three-dimensional spheroid sprouting. Consequently, pEpiSCs-derived ECs function as typical vascular ECs, indicating that pEpiSC-derived ECs might be used to develop cell therapeutics for vascular disease.