The Uridine diphosphate (UDP)-glycosyltransferases (UGTs) superfamily: the role in tumor cell metabolism

Abstract

UDP-glycosyltransferases (UGTs), important enzymes in biotransformation, control the levels and distribution of numerous endogenous signaling molecules and the metabolism of a wide range of endogenous and exogenous chemicals. The UGT superfamily in mammals consists of the UGT1, UGT2, UGT3, and UGT8 families. UGTs are rate-limiting enzymes in the glucuronate pathway, and in tumors, they are either overexpressed or underexpressed. Alterations in their metabolism can affect gluconeogenesis and lipid metabolism pathways, leading to alterations in tumor cell metabolism, which affect cancer development and prognosis. Glucuronidation is the most common mammalian conjugation pathway. Most of its reactions are mainly catalyzed by UGT1A, UGT2A and UGT2B. The body excretes UGT-bound small lipophilic molecules through the bile, urine, or feces. UGTs conjugate a variety of tiny lipophilic molecules to sugars, such as galactose, xylose, acetylglucosamine, glucuronic acid, and glucose, thereby inactivating and making water-soluble substrates, such as carcinogens, medicines, steroids, lipids, fatty acids, and bile acids. This review summarizes the roles of members of the four UGT enzyme families in tumor function, metabolism, and multiple regulatory mechanisms, and its Inhibitors and inducers. The function of UGTs in lipid metabolism, drug metabolism, and hormone metabolism in tumor cells are among the most important topics covered.

Systematic Analysis Of Expression Profiles Of SRSF Family Members For Prognostic Application In DLBCL

“…More importantly, we constructed the upstream and downstream regulatory networks of SRSF, which provided a reference for revealing the mechanism of SRSF in tumorigenesis and development. In this study, GSEA analysis showed that SRSF were mainly associated with oncogenic pathways including galactose metabolism pathway, which leading to alterations in tumor cell metabolism and affecting cancer development, growth, and survival (Liu et al, 2022). Pathway enrichment analysis indicated that the SRSF family was involved in the upregulation of tumor metabolism and metastasis, which provided novel clues for further exploration for the molecular mechanisms of SRSF in DLBCL.…”

Influence of polymorphism of enzymes of the UDP family-glucuronyl transferases on the biotransformation of tamoxifen in the therapy of luminal forms of breast cancer

“…Also, high levels of 4-OH-tamoxifen-N-glucuronide were observed in the blood plasma of UGT2B17del genotype carriers, which can be attributed to a mechanism that compensates for the higher expression of other genes in UGT2B17 del/del carriers [30]. In addition, studies have shown that the activity of UGT1A10 and UGT2B7 was reduced in malignant breast tumors compared with the corresponding enzymes in normal breast tissues [7,10,27,20]. Also, the glucuronidation activity of estradiol, the most physiologically active form of estrogen, was reduced in most cases of breast cancer compared to normal breast tissue [11,14,27].…”

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“…(Meech et al, 2015). Through glucuronidation process, UGTs weaken the biological activity of these drugs or chemical substances and increases their water solubility; hence, driving them to be eliminated in bile, urine and feces (Liu et al, 2023). Human UGTs are expressed in a wide range of organs and tissues.…”

“…Human UGTs are expressed in a wide range of organs and tissues. Mostly prominent in the liver, kidney and intestine; hence, reflecting their role in detoxification (Mazerska et al 2016;Liu et al, 2023). UGTs are also involved in epigenetic modifications such as DNA methylation and histone modifications, transcriptional regulation, post-transcriptional regulation (miRNA), and posttranslational regulation i.e.…”

“…The rise in population has laid more global burden of cancer which is continuously increasing due to the adoption of cancer-associated lifestyle such as smoking, decreased physical activity and choice of diets. As GTs are involved in the secondary metabolism and remove toxins, drugs and dangerous chemicals including carcinogens from the body through glycosylation; hence, the exacerbated glycosylation contributes towards incidence of cancer (Gupta et al, 2020;Hu et al, 2022;Pucci et al, 2022;Liu et al, 2023). There is an inhibitory metabolic effect of N-acetylglucosamine (Glc-NAc) on human prostate cancer and this was an illustration towards drug development by targeting GTs (Nishimura et al, 2012).…”