Stemness Of Human Cancer Cells Research Articles

Multiple functions of DYRK2 in cancer and tissue development.

Dual-specificity tyrosine-regulated kinases (DYRKs) are evolutionarily conserved from yeast to mammals. Accumulating studies have revealed that DYRKs have important roles in regulation of the cell cycle and survival. DYRK2, a member of the class II DYRK family protein, is a key regulator of p53, and phosphorylates it at Ser46 to induce apoptosis in response to DNA damage. Moreover, recent studies have uncovered that DYRK2 regulates G1/S transition, epithelial-mesenchymal-transition, and stemness in human cancer cells. DYRK2 also appears to have roles in tissue development in lower eukaryotes. Thus, the elucidation of mechanisms for DYRK2 during mammalian tissue development will promote the understanding of cell differentiation, tissue homeostasis, and congenital diseases as well as cancer. In this review, we discuss the roles of DYRK2 in tumor cells. Moreover, we focus on DYRK2-dependent developmental mechanisms in several species including fly (Drosophila), worm (Caenorhabditiselegans), zebrafish (Daniorerio), and mammals.

BAG3 deletion suppresses stem cell-like features of pancreatic ductal adenocarcinoma via translational suppression of ISG15

BAG3 is a member of the cochaperone BAG family and often highly expressed in various cancers. Recently, evidences show that BAG3 promotes stemness of human cancer cells. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule, which is covalently conjugated with substrates to form ISGylated proteins. Global screening BAG3 interacting partners demonstrated that ISG15 might be a potential binding partner. The current study revealed that BAG3 did not interact with ISG15, but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer (PDAC). It was further found that BAG3 deletion stabilized ISG15 mRNAs, while suppressed its translation via increasing Serine phosphorylation of Ago2 at position 387 (S387). Both BAG3 deletion and ISG15 knockdown suppressed stem cell-like phenotypes of PDAC cells, including clonogenicity, invasiveness and spheroid formation. In addition, ectopic ISG15 expression rescued the suppressive role of BAG3 deletion in cancer stem cell (CSC)-like phenotypes of PDAC cells, and this effect of ISG15 was independent of its ISGylation function. The current study implies that BAG3 and ISG15 may provide a therapeutic advantage for PDAC.