Fkbp10-KO Mouse

FKBP10, also known as FK506 binding protein 10, is a peptidyl-prolyl cis-trans isomerase (PPIase) with important functions. It is involved in multiple biological processes, such as protein translation, and is associated with pathways like hypoxia, glycolysis, and PI3K-AKT signaling. Abnormal expression of FKBP10 is related to the development of various cancers and some skeletal diseases, indicating its overall biological importance. Genetic models, including KO/CKO mouse models, are valuable for studying its functions [1-10].

In KO mouse models, deletion of Fkbp10 in osteoblasts led to qualitative defects in bone, with decreased mature, hydroxylysine-aldehyde crosslinking, reduction in mineral-to-matrix ratio and crystal size, and impaired bone biomechanical strength [7]. In disease-related studies, FKBP10 promotes the progression of clear cell renal cell carcinoma, glioma, lung cancer, colorectal cancer, stomach adenocarcinoma, and bladder cancer. In clear cell renal cell carcinoma, it enhances the Warburg effect and histone lactylation by phosphorylating LDHA [1]. In glioma, it activates the AKT-CREB-PCNA axis to promote cell proliferation [2]. In lung cancer, it boosts cancer growth and stemness via its PPIase activity and affects protein translation [3]. In colorectal cancer, circREEP3 activates FKBP10 transcription to drive tumor progression [4]. In stomach adenocarcinoma, it promotes cell proliferation, invasion, and migration by regulating the PI3K signaling pathway [5,6]. In bladder cancer, it promotes muscle invasion by dysregulating lamin A [8].

In conclusion, FKBP10 plays essential roles in protein-related processes and is involved in the development of multiple cancers and skeletal diseases. The study of Fkbp10 KO/CKO mouse models has provided insights into its functions in bone development and the pathogenesis of related diseases, highlighting its potential as a therapeutic target in cancer and other disorders.

References:

1. Liu, Ren, Zou, Zhihao, Chen, Lingwu, Wang, Zongren, Zhong, Weide. 2024. FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation. In Cell death & disease, 15, 64. doi:10.1038/s41419-024-06450-x. https://pubmed.ncbi.nlm.nih.gov/38233415/

2. Cai, Hong-Qing, Zhang, Min-Jie, Cheng, Zhi-Jian, Wang, Ming-Rong, Wan, Jing-Hai. 2021. FKBP10 promotes proliferation of glioma cells via activating AKT-CREB-PCNA axis. In Journal of biomedical science, 28, 13. doi:10.1186/s12929-020-00705-3. https://pubmed.ncbi.nlm.nih.gov/33557829/

3. Ramadori, Giorgio, Ioris, Rafael M, Villanyi, Zoltan, Collart, Martine A, Coppari, Roberto. . FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth. In Cell reports, 30, 3851-3863.e6. doi:10.1016/j.celrep.2020.02.082. https://pubmed.ncbi.nlm.nih.gov/32187554/

4. Chen, Zhenzhen, He, Luyun, Zhao, Liangbo, Zhu, Pingping, Liu, Benyu. 2022. circREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 9, e2105160. doi:10.1002/advs.202105160. https://pubmed.ncbi.nlm.nih.gov/35233964/

5. Wang, Ruo-Gu, Zhang, Dan, Zhao, Chun-Hong, Qu, Hui, He, Qing-Si. 2019. FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma. In The Kaohsiung journal of medical sciences, 36, 311-317. doi:10.1002/kjm2.12174. https://pubmed.ncbi.nlm.nih.gov/31868996/

6. Liang, Liang, Zhao, Kun, Zhu, Jin-Hui, Qin, Xin-Gan, Chen, Jun-Qiang. 2019. Comprehensive evaluation of FKBP10 expression and its prognostic potential in gastric cancer. In Oncology reports, 42, 615-628. doi:10.3892/or.2019.7195. https://pubmed.ncbi.nlm.nih.gov/31233188/

7. Lietman, Caressa D, Lim, Joohyun, Grafe, Ingo, Krakow, Deborah, Lee, Brendan H. 2017. Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone. In Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 32, 1354-1367. doi:10.1002/jbmr.3108. https://pubmed.ncbi.nlm.nih.gov/28206698/

8. Zhao, Xupeng, Wang, Jichen, Tian, Shuo, Li, Xiubin, Li, Hongzhao. 2025. FKBP10 Promotes the Muscle Invasion of Bladder Cancer via Lamin A Dysregulation. In International journal of biological sciences, 21, 758-771. doi:10.7150/ijbs.105265. https://pubmed.ncbi.nlm.nih.gov/39781460/