Cpa4-KO Mouse

Cpa4, carboxypeptidase A4, is a zinc-containing metallocarboxypeptidase. It has been implicated in various biological processes related to cancer. Although the exact associated pathways are not fully detailed in the given references, it likely participates in pathways related to cell growth, migration, and metastasis [1-10]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially be valuable for further understanding its functions.

In clear cell renal cell carcinoma (ccRCC), high Cpa4 expression is associated with worse clinical outcomes like TNM stage, and patients with high Cpa4 expression have poorer survival [1]. In non-small cell lung cancer (NSCLC), circular RNA circ-Cpa4 regulates cell growth, stemness, drug resistance, and immune evasion through the let-7 miRNA/PD-L1 axis [2]. In pancreatic cancer, Cpa4 promotes epithelial-to-mesenchymal transition (EMT) via stimulating the PI3K-AKT-mTOR signaling [3]. In endometrial cancer, Cpa4 overexpression correlates with tumor progression and poor prognosis [4]. In pancreatic cancer, Cpa4 might be a potential diagnostic serum marker [5]. In NSCLC, downregulation of Cpa4 inhibits cell growth by suppressing the AKT/c-MYC pathway [6]. Also in NSCLC, circRNA-Cpa4 promotes cell proliferation and hinders apoptosis via the miR-1183/PDPK1 axis [7]. In NSCLC, Cpa4 overexpression is associated with an unfavorable prognosis, and serum Cpa4 can aid early detection [8]. In bladder cancer, Cpa4 overexpression is linked with shorter survival and has diagnostic potential, and its expression is related to immune cell-associated genes [9]. In gastric cancer, knockdown of Cpa4 inhibits cell progression via cell cycle arrest and apoptosis [10].

In conclusion, Cpa4 plays crucial roles in the development and progression of multiple cancers, including ccRCC, NSCLC, pancreatic, endometrial, bladder, and gastric cancers. These findings from functional studies in cell lines and clinical samples highlight its significance as a potential biomarker and therapeutic target. The use of KO/CKO mouse models could further clarify its functions in these disease contexts, providing more insights into cancer-related biological processes.

References:

1. Wang, Kongjia, Ding, Yixin, Liu, Yunbo, Jiang, Bo, Hou, Sichuan. . CPA4 as a biomarker promotes the proliferation, migration and metastasis of clear cell renal cell carcinoma cells. In Journal of cellular and molecular medicine, 28, e18165. doi:10.1111/jcmm.18165. https://pubmed.ncbi.nlm.nih.gov/38494845/

2. Hong, Weijun, Xue, Min, Jiang, Jun, Zhang, Yajuan, Gao, Xiwen. 2020. Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC). In Journal of experimental & clinical cancer research : CR, 39, 149. doi:10.1186/s13046-020-01648-1. https://pubmed.ncbi.nlm.nih.gov/32746878/

3. Shao, Qingliang, Zhang, Zhiqiang, Cao, Rongxian, Pei, Wanting, Sun, Tian. 2020. CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling. In OncoTargets and therapy, 13, 8567-8580. doi:10.2147/OTT.S257057. https://pubmed.ncbi.nlm.nih.gov/32922037/

4. He, Kang, Zheng, Jingying, Zhang, Tingyu, Wu, Shan, Zhao, Lijing. 2025. CPA4 overexpression correlates with poor prognosis and tumor progression in endometrial cancer. In European journal of medical research, 30, 174. doi:10.1186/s40001-025-02293-0. https://pubmed.ncbi.nlm.nih.gov/40089797/

5. Sun, Lichao, Burnett, Joseph, Guo, Chunguang, Ran, Yuliang, Sun, Duxin. 2015. CPA4 is a promising diagnostic serum biomarker for pancreatic cancer. In American journal of cancer research, 6, 91-6. doi:. https://pubmed.ncbi.nlm.nih.gov/27073726/

6. Fu, Yangyang, Su, Lihuang, Cai, Mengsi, Wang, Liangxing, Huang, Xiaoying. 2019. Downregulation of CPA4 inhibits non small-cell lung cancer growth by suppressing the AKT/c-MYC pathway. In Molecular carcinogenesis, 58, 2026-2039. doi:10.1002/mc.23095. https://pubmed.ncbi.nlm.nih.gov/31397502/

7. Li, Heng, Lei, Yujie, Chen, Nan, Xiang, Xudong, Huang, Yunchao. 2024. circRNA-CPA4 Regulates Cell Proliferation and Apoptosis of Non-small Cell Lung Cancer via the miR-1183/PDPK1 Axis. In Biochemical genetics, 62, 4087-4102. doi:10.1007/s10528-023-10641-0. https://pubmed.ncbi.nlm.nih.gov/38273153/

8. Sun, Lichao, Wang, Yipeng, Yuan, Hebao, Myers, Ila, Sun, Duxin. 2016. CPA4 is a Novel Diagnostic and Prognostic Marker for Human Non-Small-Cell Lung Cancer. In Journal of Cancer, 7, 1197-204. doi:10.7150/jca.15209. https://pubmed.ncbi.nlm.nih.gov/27390594/

9. Wei, Chengcheng, Zhou, Yuancheng, Xiong, Qi, Yang, Xiong, Chen, Zhaohui. 2021. Comprehensive Analysis of CPA4 as a Poor Prognostic Biomarker Correlated with Immune Cells Infiltration in Bladder Cancer. In Biology, 10, . doi:10.3390/biology10111143. https://pubmed.ncbi.nlm.nih.gov/34827136/

10. Lei, Xinyi, Liu, Dong, Song, Danjun, Dai, Gaiguo, Yang, Litao. . Knockdown of carboxypeptidase A4 (CPA4) inhibits gastric cancer cell progression via cell cycle arrest and apoptosis. In Journal of gastrointestinal oncology, 13, 2823-2831. doi:10.21037/jgo-22-987. https://pubmed.ncbi.nlm.nih.gov/36636089/