The death-associated protein kinase (DAPK) family is a member of the calcium/calmodulin-regulated serine/threonine protein kinase family, and studies have shown that its role, as its name suggests, is mainly to regulate cell death. The DAPK family comprises five members, including DAPK1, DAPK2, DAPK3, DRAK1 and DRAK2, which show high homology in the common N-terminal kinase domain but differ in the extra-catalytic domain. Notably, previous research has suggested that the DAPK family plays an essential role in both the development and regulation of human diseases. However, only a few small-molecule inhibitors have been reported. In this Perspective, we mainly discuss the structure, biological function, and role of DAPKs in diseases and the currently discovered small-molecule inhibitors, providing valuable information for the development of the DAPK field.

Targeting Death-Associated Protein Kinases for Treatment of Human Diseases: Recent Advances and Future Directions.

Gastric cancer (GC) is one of the most frequently diagnosed types of cancer worldwide, and exploring its potential therapeutic targets is particularly important for improving the prognosis of patients with GC. The aim of the present study was to investigate the association between serine/threonine kinase 17a (STK17A) expression and GC prognosis. STK17A expression was measured by quantitative real‑time PCR, western blotting and immunohistochemical staining. Standard stable transfection technology was also used to construct overexpression and knockdown cell lines. Wound healing, Transwell, Cell Counting Kit‑8 and colony formation assays, as well as other methods, were used to explore the function and underlying molecular mechanism of STK17A in GC. The results indicated that STK17A overexpression significantly promoted the proliferation and migration of GC cells. The clinical significance of STK17A in a cohort of 102 cases of GC was assessed by clinical correlation and Kaplan‑Meier analyses. Overexpression of STK17A was demonstrated to be associated with tumor invasion depth (P<0.001), lymph node metastasis (P<0.001) and poor prognosis in terms of 5‑year survival (P<0.001). In addition, Cox multivariate analysis revealed that STK17A expression was an independent risk factor for overall and progress‑free survival (P<0.001). Therefore, STK17A may be a valuable biomarker for the prognosis of patients with GC.

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Shan Lin

Papers

Predictive significance of STK17A in patients with gastric cancer and association with gastric cancer cell proliferation and migration.