Systematic Review of the Role of Alpha-Protein Kinase 1 in Cancer and Cancer-Related Inflammatory Diseases

SIMPLE SUMMARY: Aside from the basic phosphorylation function of alpha-kinase 1 (ALPK1), little is known about its major functions. Researchers have used various forms of biotechnology and human, animal, and cellular models to better understand the relationship of ALPK1 with cancer and cancer-related inflammatory diseases. ALPK1 is involved in the progression of breast, lung, colorectal, oral, and skin cancer as well as lymphoblastic leukemia. ALPK1 has also been implicated in gout, diabetes, and chronic kidney disease, which are thought to be associated with breast, lung, colorectal, urinary tract, pancreatic, and endometrial cancers and lymphoblastic leukemia. ALPK1 upregulates inflammatory cytokines and chemokines during carcinogenesis. The major cytokine involved in carcinogenesis is TNF-α, which activates the NF-κB pathway, and similar inflammatory responses exist in gout, diabetes, and chronic kidney disease. ALPK1 regulates downstream inflammatory mechanisms that lead to cancer development through certain pathways and plays a key role in cancer initiation and metastasis. ABSTRACT: Background: Deregulation of conventional protein kinases is associated with the growth and development of cancer cells. Alpha-kinase 1 (ALPK1) belongs to a newly discovered family of serine/threonine protein kinases with no sequence homology to conventional protein kinases, and its function in cancer is poorly understood. Methods: In this systematic review, we searched for and analyzed studies linking ALPK1 to cancer development and progression. Results: Based on the current evidence obtained using human, animal, cellular, and tissue models, ALPK1 is located upstream and triggers cancer cell development and metastasis by regulating the inflammatory response through phosphorylation. Its mRNA and protein levels were found to correlate with advanced tumor size and lymph node metastasis, which occur from the cellular cytoplasm into the nucleus. ALPK1 is also strongly associated with gout, chronic kidney disease, and diabetes, which are considered as inflammatory diseases and associated with cancer. Conclusion: ALPK1 is an oncogene involved in carcinogenesis. Chronic inflammation is the common regulatory mechanism between cancer and these diseases. Future research should focus on identifying inhibitors of serine/threonine and ALPK1 at their phosphorylation sites, which would block various signal transductions and potentially offer kinase-targeted therapeutic agents for patients with cancer and inflammatory diseases.