GLYAT, or glycine N-acyltransferase, is an enzyme that catalyzes the transfer of acyl groups from acyl CoA to glycine, resulting in acyl glycine and coenzyme A. It is a key component of the phase II glycine conjugation pathway in the liver, playing a role in the detoxification of endogenous and xenobiotic compounds containing a carboxylic acid group, and is important for maintaining adequate levels of free coenzyme A (CoASH) [4,5,6,7].

GLYAT has been found to be lowly expressed in several cancers, including liver cancer, clear cell renal cell carcinoma (ccRCC), and breast cancer. In liver cancer and ccRCC, overexpression of GLYAT inhibits cell proliferation and migration, while interfering with GLYAT expression rescues these abilities. It was also shown to downregulate Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), suggesting that GLYAT suppresses the progression of these cancers by downregulating ROCK1 [1]. In breast cancer, knockdown of GLYAT augmented cell proliferation in vitro and in vivo, and its downregulation promoted cell migration likely through the activation of the PI3K/AKT/Snail signaling pathway, which induced epithelial-mesenchymal transition (EMT) [3].

In conclusion, GLYAT is important in metabolic detoxification pathways. Its downregulation in various cancers has been associated with tumor progression, highlighting its potential as a prognostic biomarker and therapeutic target. The functional studies in cancer cell lines and in vivo models have provided insights into its role in cancer development, suggesting that understanding GLYAT could offer new strategies for cancer treatment [1,2,3,8].

References:

1. Xia, Yechen, Huang, Wentao, Jin, Guang-Zhi. 2024. GLYAT suppresses liver cancer and clear cell renal cell carcinoma progression by downregulating ROCK1 expression. In Translational cancer research, 13, 5097-5111. doi:10.21037/tcr-24-1412. https://pubmed.ncbi.nlm.nih.gov/39430840/

2. Jiang, Fengchen, Zhou, Shuiping, Xia, Chuanlong, Dai, Feng, Fu, Shouzhong. . Downregulation of GLYAT correlates with tumour progression and poor prognosis in hepatocellular carcinoma. In Journal of cellular and molecular medicine, 28, e70197. doi:10.1111/jcmm.70197. https://pubmed.ncbi.nlm.nih.gov/39495775/

3. Tian, Xin, Wu, Lina, Jiang, Min, Liu, Caigang, Gao, Song. 2021. Downregulation of GLYAT Facilitates Tumor Growth and Metastasis and Poor Clinical Outcomes Through the PI3K/AKT/Snail Pathway in Human Breast Cancer. In Frontiers in oncology, 11, 641399. doi:10.3389/fonc.2021.641399. https://pubmed.ncbi.nlm.nih.gov/33968740/

4. Kühn, Stefan, Williams, Monray E, Dercksen, Marli, Sass, Jörn Oliver, van der Sluis, Rencia. 2023. The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation. In Computational and structural biotechnology journal, 21, 1236-1248. doi:10.1016/j.csbj.2023.01.041. https://pubmed.ncbi.nlm.nih.gov/36817957/

5. Schulke, Daniel, Sass, Jörn Oliver. 2021. Frequent sequence variants of human glycine N-acyltransferase (GLYAT) and inborn errors of metabolism. In Biochimie, 183, 30-34. doi:10.1016/j.biochi.2021.02.002. https://pubmed.ncbi.nlm.nih.gov/33567294/

6. Lino Cardenas, Christian Lacks, Bourgine, Joanna, Cauffiez, Christelle, Broly, Frank, Chevalier, Dany. 2010. Genetic polymorphisms of glycine N-acyltransferase (GLYAT) in a French Caucasian population. In Xenobiotica; the fate of foreign compounds in biological systems, 40, 853-61. doi:10.3109/00498254.2010.519407. https://pubmed.ncbi.nlm.nih.gov/20925583/

7. Badenhorst, Christoffel Petrus Stephanus, van der Sluis, Rencia, Erasmus, Elardus, van Dijk, Alberdina Aike. 2013. Glycine conjugation: importance in metabolism, the role of glycine N-acyltransferase, and factors that influence interindividual variation. In Expert opinion on drug metabolism & toxicology, 9, 1139-53. doi:10.1517/17425255.2013.796929. https://pubmed.ncbi.nlm.nih.gov/23650932/

8. Muñoz, Juan P, Calaf, Gloria M. 2023. Downregulation of Glycine N-Acyltransferase in Kidney Renal Clear Cell Carcinoma: A Bioinformatic-Based Screening. In Diagnostics (Basel, Switzerland), 13, . doi:10.3390/diagnostics13233505. https://pubmed.ncbi.nlm.nih.gov/38066746/