Taldo1-KO Mouse

TALDO1, also known as transaldolase 1, is a rate-limiting enzyme in the pentose phosphate pathway. This pathway is crucial for the production of ribose-5-phosphate for nucleotide synthesis and the generation of NADPH for antioxidant defense. The gene has two translational initiation sites, producing isoforms with differential nucleocytoplasmic distribution that regulate the global metabolic network [5].

TALDO1 has been associated with multiple diseases. In breast cancer, it was found to be an extracellular vesicle (EV) biomarker of distant metastasis, and in vitro and in vivo analysis confirmed its role in stimulating breast cancer invasion and metastasis. A TALDO1 allosteric inhibitor, AO-022, could inhibit breast cancer migration in vitro and tumor progression in vivo [1]. In hepatocellular carcinoma (HCC), TALDO1 mRNA level was higher in HCC tissues than in normal tissues, and high TALDO1 mRNA expression was an independent risk factor for prognosis. Knockdown of TALDO1 expression suppressed the proliferation and migration of HCC cells, and it was also found to negatively regulate the immune response [2]. In estrogen-receptor-positive breast cancer, TALDO1 was co-expressed with SLC1A5, and both were associated with endocrine therapy failure [3]. Mutations in TALDO1 in children were related to liver disease and an increased risk of early-onset HCC [4]. In neovascular age-related macular degeneration, the protein level of TALDO1 decreased during anti-VEGF treatment, and its reduction correlated with greater lesion regression [6]. In pulmonary arterial hypertension, TALDO1, as a glycolysis-related gene, plays an important role in the disease development [7].

In conclusion, TALDO1 is a key enzyme in the pentose phosphate pathway, and its abnormal expression is associated with various diseases such as breast cancer, HCC, estrogen-receptor-positive breast cancer, liver disease in children, neovascular age-related macular degeneration, and pulmonary arterial hypertension. Studies on TALDO1 using in vivo models like those in breast and liver cancer have provided insights into its role in disease-related biological processes, which may contribute to the development of new diagnostic and therapeutic strategies.

References:

1. Xu, Ganfei, Huang, Rui, Wumaier, Reziya, Ding, Chen, Wang, Hongxia. . Proteomic Profiling of Serum Extracellular Vesicles Identifies Diagnostic Signatures and Therapeutic Targets in Breast Cancer. In Cancer research, 84, 3267-3285. doi:10.1158/0008-5472.CAN-23-3998. https://pubmed.ncbi.nlm.nih.gov/38900939/

2. Cen, Kedan, Lu, Caide. 2023. Prognostic and Immune Infiltration Analysis of Transaldolase 1 (TALDO1) in Hepatocellular Carcinoma. In International journal of general medicine, 16, 5779-5788. doi:10.2147/IJGM.S425490. https://pubmed.ncbi.nlm.nih.gov/38089714/

3. Alfarsi, Lutfi H, El Ansari, Rokaya, Craze, Madeleine L, Rakha, Emad A, Green, Andrew R. 2021. SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer. In Breast cancer research and treatment, 189, 317-331. doi:10.1007/s10549-021-06298-1. https://pubmed.ncbi.nlm.nih.gov/34282517/

4. Grammatikopoulos, Tassos, Hadzic, Nedim, Foskett, Pierre, Bull, Laura N, Thompson, Richard J. 2021. Liver Disease and Risk of Hepatocellular Carcinoma in Children With Mutations in TALDO1. In Hepatology communications, 6, 473-479. doi:10.1002/hep4.1824. https://pubmed.ncbi.nlm.nih.gov/34677006/

5. Moriyama, Tetsuji, Tanaka, Shu, Nakayama, Yasumune, Fukusaki, Eiichiro, Oka, Masahiro. 2016. Two isoforms of TALDO1 generated by alternative translational initiation show differential nucleocytoplasmic distribution to regulate the global metabolic network. In Scientific reports, 6, 34648. doi:10.1038/srep34648. https://pubmed.ncbi.nlm.nih.gov/27703206/

6. Zhuang, Xuenan, Li, Miaoling, Mi, Lan, Chen, Xuelin, Wen, Feng. . Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging. In Investigative ophthalmology & visual science, 65, 24. doi:10.1167/iovs.65.10.24. https://pubmed.ncbi.nlm.nih.gov/39140961/

7. Lou, Yu-Xuan, Shi, Er-Dan, Yang, Rong, Yang, Yang. . Exploring the mechanisms of glycolytic genes involvement in pulmonary arterial hypertension through integrative bioinformatics analysis. In Journal of cellular and molecular medicine, 28, e18447. doi:10.1111/jcmm.18447. https://pubmed.ncbi.nlm.nih.gov/38837574/