Akr1b10-KO Mouse

Akr1b10, an aldo-keto reductase, is a human nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase belonging to the AKR1B subfamily. It catalyzes the reduction of aldehydes, some ketones and quinones, and interacts with acetyl-CoA carboxylase and heat shock protein 90α [4]. It is highly expressed in epithelial cells of the stomach and intestine, but its expression patterns vary in different diseases. It is down-regulated in gastrointestinal cancers and inflammatory bowel diseases, while up-regulated in many cancers, non-alcoholic fatty liver disease and some skin diseases [4].

In breast cancer, overexpression of Akr1b10 promotes cell proliferation, migration and invasion via the PI3K/AKT/NF-κB signaling pathway and activation of ERK signaling. Knockdown of Akr1b10 in BT-20 cells inhibits these effects [1,2]. In lung cancer-derived brain metastasis, silencing Akr1b10 in resistant cells increases sensitivity to pemetrexed. Akr1b10 enhances the Warburg effect, facilitating glycolysis, which is vital for acquired resistance [3].

In summary, Akr1b10 plays a crucial role in cancer-related biological processes. Studies using gene knockdown models in cell lines and in vivo tumor xenograft experiments have revealed its roles in promoting breast cancer growth and metastasis, as well as contributing to acquired chemoresistance in lung cancer brain metastasis. These findings suggest Akr1b10 could be a potential prognostic indicator and therapeutic target in cancer treatment.

References:

1. Qu, Jiayao, Li, Jia, Zhang, Yaming, Xia, Chenglai, Luo, Dixian. 2021. AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway. In Cell & bioscience, 11, 163. doi:10.1186/s13578-021-00677-3. https://pubmed.ncbi.nlm.nih.gov/34419144/

2. Li, Jia, Guo, Yuanwei, Duan, Lili, Zhu, Yuan-Shan, Luo, Di-Xian. . AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling. In Oncotarget, 8, 33694-33703. doi:10.18632/oncotarget.16624. https://pubmed.ncbi.nlm.nih.gov/28402270/

3. Duan, Wenzhe, Liu, Wenwen, Xia, Shengkai, Li, Xinyu, Wang, Qi. 2023. Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis. In Journal of translational medicine, 21, 547. doi:10.1186/s12967-023-04403-0. https://pubmed.ncbi.nlm.nih.gov/37587486/

4. Endo, Satoshi, Matsunaga, Toshiyuki, Nishinaka, Toru. 2021. The Role of AKR1B10 in Physiology and Pathophysiology. In Metabolites, 11, . doi:10.3390/metabo11060332. https://pubmed.ncbi.nlm.nih.gov/34063865/