Casein kinase 2 (CK2) has become a potential therapeutic target in gastric cancer; however, the underlying mechanism remains incompletely understood. TAp73, a structural homolog of the tumor suppressor p53, acts as a critical regulator of the Warburg effect. Recent study reveals that aberrant CK2 signaling is able to inhibit TAp73 function. Here we determine that TAp73 is overexpressed in AGS-1 but not in SNU-5 gastric cancer cell line as compared with normal gastric cells. In addition, we show that TAp73 expression is required for the maintenance of glucose uptake and lactate release in AGS-1 but not in SNU-5 gastric cancer cells. Importantly, the use of CX-4945, a selective inhibitor of protein kinase CK2, inhibits cell growth and invasion, and promotes cell apoptosis in AGS-1 with decreased TAp73 expression as well as downregulated glucose uptake and lactate release. Although TAp73 knockdown resulted in significant decreases in TAp73 expressions in SNU-5 cell line, no differences in glucose uptake and lactate release were observed between SNU-5 and normal gastric cells. Moreover, TAp73 gene overexpression promotes glucose uptake and lactate release and abolishes the anti-cancer effects of CX-4945 in gastric cancer cell line AGS-1. The impacts of CX-4945 on glycolysis and tumorigenesis were strongly limited in SNU-5 gastric cancer cell line. These findings suggest that CX-4945 elicits an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibits gastric tumorigenesis.

酪蛋白激酶2（CK2）已成为胃癌的潜在治疗靶点。但是，底层机制仍未完全理解。TAp73是肿瘤抑制因子p53的结构同源物，是Warburg效应的关键调节剂。最近的研究表明，异常的CK2信号传导能够抑制TAp73功能。在这里，我们确定与正常胃细胞相比，TAp73在AGS-1中过表达，但在SNU-5胃癌细胞中没有过表达。此外，我们表明，TAp73表达对于维持AGS-1中的葡萄糖摄取和乳酸释放是必需的，而不是在SNU-5胃癌细胞中。重要的是，使用蛋白激酶CK2的选择性抑制剂CX-4945可抑制细胞生长和侵袭，并通过降低TAp73表达以及下调葡萄糖摄取和乳酸释放来促进AGS-1中的细胞凋亡。尽管TAp73敲低导致SNU-5细胞系中TAp73表达显着降低，但在SNU-5和正常胃细胞之间未观察到葡萄糖摄取和乳酸释放的差异。此外，TAp73基因过表达促进葡萄糖摄取和乳酸释放，并消除了CX-4945在胃癌细胞系AGS-1中的抗癌作用。在SNU-5胃癌细胞系中，强烈限制了CX-4945对糖酵解和肿瘤发生的影响。这些发现表明CX-4945在过表达Tap73的胃癌中引发抗Warburg效应，并抑制胃肿瘤的发生。尽管TAp73敲低导致SNU-5细胞系中TAp73表达显着降低，但在SNU-5和正常胃细胞之间未观察到葡萄糖摄取和乳酸释放的差异。此外，TAp73基因过表达促进葡萄糖摄取和乳酸释放，并消除了CX-4945在胃癌细胞系AGS-1中的抗癌作用。在SNU-5胃癌细胞系中，强烈限制了CX-4945对糖酵解和肿瘤发生的影响。这些发现表明CX-4945在过表达Tap73的胃癌中引发抗Warburg效应，并抑制胃肿瘤的发生。尽管TAp73敲低导致SNU-5细胞系中TAp73表达显着降低，但在SNU-5和正常胃细胞之间未观察到葡萄糖摄取和乳酸释放的差异。此外，TAp73基因过表达促进葡萄糖摄取和乳酸释放，并消除了CX-4945在胃癌细胞系AGS-1中的抗癌作用。在SNU-5胃癌细胞系中，强烈限制了CX-4945对糖酵解和肿瘤发生的影响。这些发现表明CX-4945在过表达Tap73的胃癌中引发抗Warburg效应，并抑制胃肿瘤的发生。TAp73基因过表达促进葡萄糖摄取和乳酸释放，并废除了CX-4945在胃癌细胞系AGS-1中的抗癌作用。在SNU-5胃癌细胞系中，强烈限制了CX-4945对糖酵解和肿瘤发生的影响。这些发现表明CX-4945在过表达Tap73的胃癌中引发抗Warburg效应并抑制胃肿瘤的发生。TAp73基因过表达促进葡萄糖摄取和乳酸释放，并废除了CX-4945在胃癌细胞系AGS-1中的抗癌作用。在SNU-5胃癌细胞系中，强烈限制了CX-4945对糖酵解和肿瘤发生的影响。这些发现表明CX-4945在过表达Tap73的胃癌中引发抗Warburg效应并抑制胃肿瘤的发生。