Year: 2021
Type: review
Abstract: through its EF-hand motifs and tyrosine phosphorylation. DGKα is highly expressed in several refractory cancer cells including melanoma, hepatocellular carcinoma, and glioblastoma cells. In melanoma cells, DGKα is an antiapoptotic factor that activates nuclear factor-κB (NF-κB) through the atypical protein kinase C (PKC) ζ-mediated phosphorylation of NF-κB. DGKα acts as an enhancer of proliferative activity through the Raf-MEK-ERK pathway and consequently exacerbates hepatocellular carcinoma progression. In glioblastoma and melanoma cells, DGKα attenuates apoptosis by enhancing the phosphodiesterase (PDE)-4A1-mammalian target of the rapamycin pathway. As PA activates PKCζ, Raf, and PDE, it is likely that PA generated by DGKα plays an important role in the proliferation/antiapoptosis of cancer cells. In addition to cancer cells, DGKα is highly abundant in T cells and induces a nonresponsive state (anergy), which represents the main mechanism by which advanced cancers escape immune action. In T cells, DGKα attenuates the activity of Ras-guanyl nucleotide-releasing protein, which is activated by DG and avoids anergy through DG consumption. Therefore, a DGKα-specific inhibitor is expected to be a dual effective anticancer treatment that inhibits cancer cell proliferation and simultaneously enhances T cell functions. Moreover, the inhibition of DGKα synergistically enhances the anticancer effects of programmed cell death-1/programmed cell death ligand 1 blockade. Taken together, DGKα inhibition provides a promising new treatment strategy for refractory cancers.
Source: Cancers
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,376
Funders: Uehara Memorial Foundation, Ministry of Education, Culture, Sports, Science and Technology, Tojuro Iijima Foundation for Food Science and Technology, SENSHIN Medical Research Foundation, Japan Food Chemical Research Foundation, Japan Society for the Promotion of Science, Japan Science and Technology Agency
Awards: G1131105725, G1379623095, Structural basis for enzymatic catalysis and regulation of diacylglycerol kinase alpha, G2302691157, Identification of new diacylglycerol phosphorylation pathways and their molecular machinery, G3888539577, G46250814, Molecular mechanisms of novel diacylglycerol phosphorylation pathways that control various physiological and pathological phenomena, G5339581405, Identification of novel pathways consist of DGK isozymes using new analyzing methods and regulation of their functions, Identification of trace bioactive lipid, phosphatidic acid molecular species: approaching physiological significance of lipid diversities, Identification of phosphatidylcholine-specifc phospholipase C, Regulation mechanisms of diacylglycerol kinase delta in differentiation and development of skeletal muscle to prevent exaggeration of type 2 diabetes, G696277500, ジアシルグリセロールキナーゼαの発現・活性抑制により免疫力を増進する体内・食品成分の探索・同定―新興・再興感染症やがん等に持続的抵抗性を持つ体質への改善の試み―
OpenAlex ID: W3205653438