PTGES, also known as prostaglandin E synthase, is a key enzyme in the arachidonic acid pathway responsible for the synthesis of prostaglandin E2 (PGE2) [1-5, 7-10]. PGE2 is involved in multiple biological processes such as inflammation, cell growth, and immune regulation [1-5, 7-10]. PTGES-related pathways are also associated with lipid metabolism and metabolic reprogramming [1,2,4,7,8].

In lung cancer, PTGES promotes myofibroblast differentiation via the HIF-1α-dependent glycolysis pathway, contributing to fibrosis and disease progression [1]. In colorectal cancer, targeting the PTGES/PGE2 axis enhances the sensitivity of cancer cells to 5-fluorouracil [2]. In Gprc5a-knockout mouse models, Ptges-knockout in lung tumor cells reduces their tumorigenicity and lung metastasis mainly through immunosuppression [3]. In pancreatic ductal adenocarcinoma, PTGES expression is associated with metabolic and immune reprogramming [4]. In non-small cell lung cancer, the upregulated USP9X-PTGES-PGE2 axis promotes metastatic features [5]. In osteosarcoma, FUBP1 confers lobaplatin resistance by transcriptionally activating PTGES and facilitating the arachidonic acid metabolic pathway [6].

In conclusion, PTGES plays a crucial role in various diseases, especially in cancer-related processes like tumor growth, metastasis, and drug resistance. The study of PTGES knockout or conditional knockout mouse models has significantly contributed to understanding its functions in these disease conditions, providing potential therapeutic targets for treatment [1-5, 8].

References:

1. Lin, Min-Hsi, Lee, Yi-Chen, Liao, Jia-Bin, Chou, Chih-Yu, Yang, Yi-Fang. . PTGES is involved in myofibroblast differentiation via HIF-1α-dependent glycolysis pathway. In Journal of cellular and molecular medicine, 28, e70157. doi:10.1111/jcmm.70157. https://pubmed.ncbi.nlm.nih.gov/39417702/

2. Geng, Song, Zhan, Hao, Cao, Lianmeng, Geng, Longlong, Ren, Xiang. 2023. Targeting PTGES/PGE2 axis enhances sensitivity of colorectal cancer cells to 5-fluorouracil. In Biochemistry and cell biology = Biochimie et biologie cellulaire, 101, 501-512. doi:10.1139/bcb-2023-0101. https://pubmed.ncbi.nlm.nih.gov/37358009/

3. Wang, Tong, Jing, Bo, Xu, Dongliang, Zhou, Binhua P, Deng, Jiong. 2020. PTGES/PGE2 signaling links immunosuppression and lung metastasis in Gprc5a-knockout mouse model. In Oncogene, 39, 3179-3194. doi:10.1038/s41388-020-1207-6. https://pubmed.ncbi.nlm.nih.gov/32060421/

4. Murthy, Divya, Attri, Kuldeep S. 2023. PTGES Expression Is Associated with Metabolic and Immune Reprogramming in Pancreatic Ductal Adenocarcinoma. In International journal of molecular sciences, 24, . doi:10.3390/ijms24087304. https://pubmed.ncbi.nlm.nih.gov/37108468/

5. Wang, Tong, Jing, Bo, Sun, Beibei, Zhou, Binhua P, Deng, Jiong. 2019. Stabilization of PTGES by deubiquitinase USP9X promotes metastatic features of lung cancer via PGE2 signaling. In American journal of cancer research, 9, 1145-1160. doi:. https://pubmed.ncbi.nlm.nih.gov/31285948/

6. Ma, Qiong, Sun, Jin, Wang, Huan, Gong, Li, Zhang, Wei. 2023. Far upstream element-binding protein 1 confers lobaplatin resistance by transcriptionally activating PTGES and facilitating the arachidonic acid metabolic pathway in osteosarcoma. In MedComm, 4, e257. doi:10.1002/mco2.257. https://pubmed.ncbi.nlm.nih.gov/37180822/

7. Ding, Xuexuan, Qin, Jingtong, Huang, Fangfang, Feng, Fuhai, Luo, Lianxiang. 2023. The combination of machine learning and untargeted metabolomics identifies the lipid metabolism -related gene CH25H as a potential biomarker in asthma. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 72, 1099-1119. doi:10.1007/s00011-023-01732-0. https://pubmed.ncbi.nlm.nih.gov/37081162/

8. Ma, Seongho, Yeom, Jiah, Lim, Young-Hee. 2020. Exogenous NAD+ Stimulates MUC2 Expression in LS 174T Goblet Cells via the PLC-Delta/PTGES/PKC-Delta/ERK/CREB Signaling Pathway. In Biomolecules, 10, . doi:10.3390/biom10040580. https://pubmed.ncbi.nlm.nih.gov/32283838/