Aldob, short for fructose-1,6-bisphosphate aldolase B, is a glycolytic enzyme. It plays a crucial role in glucose metabolism, participating in pathways such as glycolysis and gluconeogenesis. Its function in these metabolic processes is essential for maintaining normal cellular energy homeostasis. Genetic models, like gene knockout (KO) mouse models, are valuable for studying Aldob's function in vivo [2].

In hepatocellular carcinogenesis, liver-specific Aldob knockout mice showed that Aldob downregulation was negatively correlated with CD8 + T cell infiltration in tumor tissues, and Aldob deficiency in tumor cells upregulated TGF-β expression, increasing Treg cells and impairing CD8 + T cell activity. The combination of low Aldob and high TGF-β expression led to the worst overall survival for HCC patients, and blocking TGF-β and PD-1 additively inhibited tumorigenesis induced by Aldob deficiency [1]. In gastric cancer, loss-of-function studies indicated that Aldob inhibited the growth and migrative ability of cancer cells, as its downregulation was linked to tumor size, invasion, metastasis, and poor prognosis. Aldob was shown to modulate the AKT signaling pathway [3]. In clear cell renal cell carcinoma (ccRCC), analysis of multiple databases revealed that Aldob expression was down-regulated, and it was correlated with T stage, M stage, and histologic grade. Survival analysis showed it was an independent predictor of overall survival, disease-specific survival, and progression-free survival. Functional enrichment analysis suggested its involvement in metabolism-related pathways [4].

In conclusion, Aldob is a key glycolytic enzyme involved in important metabolic pathways. Studies using KO mouse models and other loss-of-function experiments have revealed its significance in various cancer-related processes, such as immune evasion in hepatocellular carcinoma, growth and metastasis in gastric cancer, and prognosis in clear cell renal cell carcinoma. These findings contribute to our understanding of the role of Aldob in disease development and potentially guide new therapeutic strategies.

References:

1. Yin, Chunzhao, Zhang, Cunzhen, Wang, Yongqiang, Tao, Yongzhen, Yin, Huiyong. 2023. ALDOB/KAT2A interactions epigenetically modulate TGF-β expression and T cell functions in hepatocellular carcinogenesis. In Hepatology (Baltimore, Md.), 81, 77-93. doi:10.1097/HEP.0000000000000704. https://pubmed.ncbi.nlm.nih.gov/38051951/

2. Herman, Mark A, Birnbaum, Morris J. 2021. Molecular aspects of fructose metabolism and metabolic disease. In Cell metabolism, 33, 2329-2354. doi:10.1016/j.cmet.2021.09.010. https://pubmed.ncbi.nlm.nih.gov/34619074/

3. Peng, Chaozhong, Yang, Xuan, Li, Xiao, Wang, Jiangming, Wu, Wenqing. 2023. ALDOB plays a tumor-suppressive role by inhibiting AKT activation in gastric cancer. In Journal of Cancer, 14, 2255-2262. doi:10.7150/jca.83456. https://pubmed.ncbi.nlm.nih.gov/37576390/

4. Shao, Yuan, Wu, Bo, Yang, Zhen, Wang, Yong, Niu, Yuanjie. . ALDOB represents a potential prognostic biomarker for patients with clear cell renal cell carcinoma. In Translational andrology and urology, 12, 549-571. doi:10.21037/tau-22-743. https://pubmed.ncbi.nlm.nih.gov/37181232/