Academic Journal
CYP3A5 unexpectedly regulates glucose metabolism through the AKT–TXNIP–GLUT1 axis in pancreatic cancer
| Title: | CYP3A5 unexpectedly regulates glucose metabolism through the AKT–TXNIP–GLUT1 axis in pancreatic cancer |
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| Authors: | Ming Shao, Qingfei Pan, Haiyan Tan, Jing Wu, Ha Won Lee, Andrew D. Huber, William C. Wright, Ji-Hoon Cho, Jiyang Yu, Junmin Peng, Taosheng Chen |
| Source: | Genes and Diseases, Vol 11, Iss 4, Pp 101079- (2024) |
| Publisher Information: | KeAi Communications Co., Ltd., 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Medicine (General) LCC:Genetics |
| Subject Terms: | Cell migration, CYP3A5, Glucose metabolism, GLUT1, Pancreatic cancer, TXNIP, Medicine (General), R5-920, Genetics, QH426-470 |
| More Details: | CYP3A5 is a cytochrome P450 (CYP) enzyme that metabolizes drugs and contributes to drug resistance in cancer. However, it remains unclear whether CYP3A5 directly influences cancer progression. In this report, we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal adenocarcinoma. Multi-omics analysis showed that CYP3A5 knockdown results in a decrease in various glucose-related metabolites through its effect on glucose transport. A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP, a negative regulator of GLUT1. Notably, CYP3A5-generated reactive oxygen species were proved to be responsible for attenuating the AKT–4EBP1–TXNIP signaling pathway. CYP3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic cancer. Taken together, our results, for the first time, reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2352-3042 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2352304223003628; https://doaj.org/toc/2352-3042 |
| DOI: | 10.1016/j.gendis.2023.101079 |
| Access URL: | https://doaj.org/article/9ad3267c458a4173bd3a65ec2f9de8f9 |
| Accession Number: | edsdoj.9ad3267c458a4173bd3a65ec2f9de8f9 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23523042 |
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| DOI: | 10.1016/j.gendis.2023.101079 |
| Published in: | Genes and Diseases |
| Language: | English |