olopatadine hcl mg DGKs are a family of

DGKs are a family of enzymes which phosphorylate diacylglycerol (DAG) and convert it to phosphatidic olopatadine hcl mg (PA) [7]. DAG is an established activator of the conventional and novel protein kinase Cs, Ras guanyl nucleotide-releasing protein, Unc-13 and chimaerin [8], [9]. PA has also been reported to control a variety of important signaling proteins, such as phosphatidylinositol-4-phosphate 5-kinase, son of sevenless, Ras GTPase-activating protein, C-Raf and atypical protein kinase C [10]. Therefore, DGKs play a pivotal role in a variety of intracellular signaling by modulating the balance between two bioactive lipids, DAG and PA. To date, a total of ten mammalian DGK isozymes (α–κ) have been identified [11]. These isozymes share two or three characteristic zinc finger-like C1 domains and the catalytic region of the enzyme in common. DGK are divided into five groups according to their structural features. DGKγ belongs to the type I DGKs, containing two sets of Ca2+-binding EF-hand motifs at their N-termini [12]. DGKγ also functions as an upstream suppressor of Rac1 through its catalytic action [13], [14]. It has been reported that DGKγ is epigenetically silenced in colorectal cancer, suggesting that DGKγ may act as a tumor suppressor [15]. However, the function of DGKγ in cancer biology is still not well understood. Cancer cells exhibit profound alterations in their metabolism, mainly characterized by two major changes: Warburg effect, or aerobic glycolysis, and an increased dependence on glutamine [16], [17], [18]. As key metabolic substrates in cancer cells, both glucose and glutamine are critical for cancer development, invasion, and metastases [19], [20], [21]. Previous studies have demonstrated that elevated expression of glucose transporters has been observed in most cancers [20]. Moreover, increased glucose transporter 1 (GLUT1) expression levels in HCC cells functionally promote tumorigenicity [23].
Materials and methods
Results
Discussion Based on our results, we found that DGKγ functioned differently in SNU449 and SK-Hep1 cell lines. DGKγ inhibited cell migration in both SNU449 and SK-Hep1 cell lines, while DGKγ inhibited cell proliferation significantly in SNU449 but marginally in SK-Hep1. The different origin of the two cell lines may attribute to the difference. Because SNU449 in an HCC cell line while SK-Hep1 is derived from liver adenocarcinoma. Furthermore, we found that kinase-dead DGKγ inhibited cell migration but not cell proliferation of HCC cells, indicating that DGKγ inhibited cell migration independent of its kinase activity, and DGKγ inhibited cell migration and proliferation via different pathways. Rac1 is a master regulator of the cytoskeleton and cell motility [33]. It was previously reported that DGKγ acts as an upstream suppressor for Rac1 by activating β2-chimaerin, a Rac-specific GAP, dependent on its kinase activity [13], [14]. In this study, the results showed that DGKγ inhibited cell migration independent of Rac1. DGKγ may suppress cell migration by inhibiting EMT of HCC cells but the mechanism remains unclear.