Peng Chaozhong, Yang Xuan, Li Xiao, Ye Zhixue, Wang Jiangming, Wu Wenqing
Department of General Surgery, Suzhou Wuzhong People's Hospital, Suzhou 215128, Jiangsu, China.
Department of Gastroenterology, Suzhou Wuzhong People's Hospital, Suzhou 215128, Jiangsu, China.
J Cancer. 2023 Jul 16;14(12):2255-2262. doi: 10.7150/jca.83456. eCollection 2023.
Enhanced aerobic glycolysis has been one of the cancer hallmarks. Cancerous cells develop certain alterations during glucose metabolism for supporting their infinite growth requirement and metastasis. Therefore, targeting metabolism, for instance, crucial glycolytic enzymes, will provide a novel therapeutic strategy to treat cancer. Aldolase B (ALDOB), as a glycolytic enzyme, plays a contentious role in cancers and can either act against the tumor or as an oncogenic enzyme. The precise role of ALDOB in gastric cancer (GC) and the endogenous process is elusive and needs further exploration. This investigation revealed that ALDOB expression was markedly decreased in GC tissues. Furthermore, ALDOB inhibition was notably linked with tumor size, depth of tumor invasion, lymph node metastasis (LNM), tumor node metastases (TNM) staging, and substandard prognosis of GC. The assessment of loss- and gain-of-function indicated that ALDOB inhibited the growth and the migrative ability of GC cells, suggesting its anti-tumor role. Mechanistic studies revealed that ALDOB modulates the AKT signaling pathway. The increase in growth and cells' ability to migrate stimulated by ALDOB inhibition was partially impaired in cells under the influence of AKT inhibitors. The overall data highlights a novel target, the ALDOB/AKT signaling axis for the treatment of GC.
增强的有氧糖酵解一直是癌症的特征之一。癌细胞在葡萄糖代谢过程中会发生某些改变，以满足其无限生长和转移的需求。因此，针对代谢，例如关键的糖酵解酶，将为治疗癌症提供一种新的治疗策略。醛缩酶B（ALDOB）作为一种糖酵解酶，在癌症中发挥着有争议的作用，它既可以对抗肿瘤，也可以作为一种致癌酶。ALDOB在胃癌（GC）中的精确作用以及内源性过程尚不清楚，需要进一步探索。本研究表明，GC组织中ALDOB的表达明显降低。此外，ALDOB的抑制与肿瘤大小、肿瘤浸润深度、淋巴结转移（LNM）、肿瘤淋巴结转移（TNM）分期以及GC的不良预后显著相关。功能丧失和功能获得评估表明，ALDOB抑制GC细胞的生长和迁移能力，提示其抗肿瘤作用。机制研究表明，ALDOB调节AKT信号通路。在AKT抑制剂的影响下，细胞中由ALDOB抑制刺激的生长增加和细胞迁移能力部分受损。总体数据突出了一个新的靶点，即ALDOB/AKT信号轴用于治疗GC。
