Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of Oncology, The Affiliated Huai'an Hospital of Xuzhou Medical University and The second People's Hospital of Huai'an, Huai'an, 223002, China.
Cell Death Dis. 2022 Feb 2;13(2):99. doi: 10.1038/s41419-022-04575-5.
Transketolase (TKT) which is an important metabolic enzyme in the pentose phosphate pathway (PPP) participates in maintaining ribose 5-phosphate levels. TKT is necessary for maintaining cell growth. However, we found that in addition to this, TKT can also affect tumor progression through other ways. Our previous study indicate that TKT could promote the development of liver cancer by affecting bile acid metabolism. And in this study, we discovered that TKT expression was remarkably upregulated in colorectal cancer, abnormal high expression of TKT is associated with poor prognosis of colorectal cancer. Additionally, TKT promoted colorectal cancer cell growth and metastasis. Further study demonstrated that TKT interacted with GRP78 and promoted colorectal cancer cell glycolysis through increasing AKT phosphorylation, thereby enhancing colorectal cancer cell metastasis. Thus, TKT is expected to become an indicator for judging the prognosis of colorectal cancer, and provide a theoretical basis for drug development of new treatment targets for colorectal cancer.
转酮醇酶(TKT)是戊糖磷酸途径(PPP)中的一种重要代谢酶,参与维持核糖 5-磷酸水平。TKT 对于维持细胞生长是必需的。然而,我们发现,除了这一点之外,TKT 还可以通过其他方式影响肿瘤的进展。我们之前的研究表明,TKT 通过影响胆汁酸代谢促进肝癌的发展。在这项研究中,我们发现 TKT 在结直肠癌中表达显著上调,TKT 的异常高表达与结直肠癌的不良预后相关。此外,TKT 促进结直肠癌细胞的生长和转移。进一步的研究表明,TKT 通过增加 AKT 磷酸化与 GRP78 相互作用,从而促进结直肠癌细胞的糖酵解,增强结直肠癌细胞的转移。因此,TKT 有望成为判断结直肠癌预后的指标,并为结直肠癌新治疗靶点药物的开发提供理论依据。