Aldh1l1, also known as cytosolic 10-formyltetrahydrofolate dehydrogenase, is a key regulatory enzyme in folate metabolism. It controls the overall flux of one-carbon groups in folate-dependent biosynthetic pathways, which are vital for nucleic acid biosynthesis, DNA repair, methylation processes, amino acid biogenesis, and energy balance [1,3].

In cancer research, the loss of Aldh1l1 is significant. In a diethylnitrosamine (DEN) model of liver carcinogenesis, Aldh1l1 knockout (Aldh1l1-/-) mice showed accelerated growth of larger tumors compared to wild-type (Aldh1l1 + / + ) mice, without affecting tumor initiation or multiplicity, suggesting that Aldh1l1 loss promotes malignant tumor growth [4]. Also, re-expression of Aldh1l1 in cancer cells leads to inhibition of proliferation, apoptosis, and affects migration and invasion through a folate-dependent mechanism, indicating its role as a candidate tumor suppressor [2].

In conclusion, Aldh1l1 is essential for regulating folate-dependent biosynthetic pathways. The study of Aldh1l1 knockout mouse models has revealed its potential role in tumor suppression, especially in liver cancer. Understanding Aldh1l1's function through these in vivo models provides insights into the metabolic mechanisms underlying cancer development, which may contribute to the development of new cancer therapies [2,4].

References:

1. Krupenko, Sergey A, Krupenko, Natalia I. . ALDH1L1 and ALDH1L2 Folate Regulatory Enzymes in Cancer. In Advances in experimental medicine and biology, 1032, 127-143. doi:10.1007/978-3-319-98788-0_10. https://pubmed.ncbi.nlm.nih.gov/30362096/

2. Krupenko, Sergey A, Krupenko, Natalia I. 2019. Loss of ALDH1L1 folate enzyme confers a selective metabolic advantage for tumor progression. In Chemico-biological interactions, 302, 149-155. doi:10.1016/j.cbi.2019.02.013. https://pubmed.ncbi.nlm.nih.gov/30794800/

3. Krupenko, Sergey A, Horita, David A. 2019. The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1. In Frontiers in genetics, 10, 1013. doi:10.3389/fgene.2019.01013. https://pubmed.ncbi.nlm.nih.gov/31737034/

4. Krupenko, Natalia I, Sharma, Jaspreet, Fogle, Halle M, Sumner, Susan, Krupenko, Sergey A. 2021. Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis. In Cancers, 13, . doi:10.3390/cancers13133219. https://pubmed.ncbi.nlm.nih.gov/34203215/