Upk1b, a member of the uroplakin family, encodes a membrane-spanning protein highly specific to the urothelium. Uroplakins form urothelial plaques on the apical membrane of umbrella cells in the urothelium, providing a barrier to prevent urine passage across the renal pelvis, ureters, and bladder. They are also involved in nephrogenesis [7].

In urothelial carcinoma of the bladder, a progressive loss of Upk1b expression is linked to stage progression. Low Upk1b expression is associated with high-grade, invasive tumor growth, and nodal metastasis [5,6]. In non-small cell lung cancer (NSCLC), Upk1B promotes the proliferation, invasion, and stem cell characteristics of NSCLCs by activating the c-myc/Sox4 axis [1]. In bladder cancer, Upk1B promotes the invasion and metastasis via regulating the Wnt/β-catenin pathway [2]. In renal cell carcinoma, NAA10 promotes cell proliferation by upregulating Upk1B [3]. In gastric cancer, Upk1B is significantly upregulated, promoting tumor progression, and is correlated with worse clinical outcomes, including advanced stages and reduced survival rates [4,8].

In conclusion, Upk1b is crucial for maintaining the normal function of the urothelium. Its dysregulation is associated with the development and progression of multiple cancers, such as urothelial carcinoma, NSCLC, bladder cancer, renal cell carcinoma, and gastric cancer. Studies on Upk1b knockout or knockdown models in these cancer types have provided insights into its role in promoting tumor-related biological processes, highlighting its potential as a diagnostic and therapeutic target.

References:

1. Liu, Yiyang, Ding, Li, Li, Chunwei, Chen, Jianjun, Hou, Yulong. 2023. UPK1B promoted the invasion and stem cell characteristics of non-small cell lung cancer cells by modulating c-myc/Sox4 axis. In Tissue & cell, 85, 102250. doi:10.1016/j.tice.2023.102250. https://pubmed.ncbi.nlm.nih.gov/37866150/

2. Wang, F-H, Ma, X-J, Xu, D, Luo, J. . UPK1B promotes the invasion and metastasis of bladder cancer via regulating the Wnt/β-catenin pathway. In European review for medical and pharmacological sciences, 22, 5471-5480. doi:10.26355/eurrev_201809_15807. https://pubmed.ncbi.nlm.nih.gov/30229818/

3. Zhang, Z-Y, Zhang, J-L, Zhao, L-X, Liu, Y-R, Zheng, G-P. . NAA10 promotes proliferation of renal cell carcinoma by upregulating UPK1B. In European review for medical and pharmacological sciences, 24, 11553-11560. doi:10.26355/eurrev_202011_23796. https://pubmed.ncbi.nlm.nih.gov/33275221/

4. Zhu, Haixing, Jiang, Wen, Zhang, Qian, Yu, Changjun. 2025. The role of UPK1B in gastric cancer: multi-omics analysis and experimental validation. In Discover oncology, 16, 476. doi:10.1007/s12672-025-02263-2. https://pubmed.ncbi.nlm.nih.gov/40189715/

5. Kaczmarek, Krystian, Plage, Henning, Furlano, Kira, Horst, David, Zecha, Henrik. 2023. Loss of Upk1a and Upk1b expression is linked to stage progression in urothelial carcinoma of the bladder. In International urology and nephrology, 56, 499-508. doi:10.1007/s11255-023-03800-0. https://pubmed.ncbi.nlm.nih.gov/37777995/

6. Reiswich, Viktor, Akdeniz, Gonca, Lennartz, Maximilian, Krech, Till, Dum, David. 2022. Large-scale human tissue analysis identifies Uroplakin 1b as a putative diagnostic marker in surgical pathology. In Human pathology, 126, 108-120. doi:10.1016/j.humpath.2022.05.002. https://pubmed.ncbi.nlm.nih.gov/35550834/

7. Sivakumaar, Krithicck, Griffin, Jon, Schofield, Ella, Catto, James W F, Jubber, Ibrahim. 2024. Gene of the month: the uroplakins. In Journal of clinical pathology, 77, 291-296. doi:10.1136/jcp-2024-209388. https://pubmed.ncbi.nlm.nih.gov/38418202/

8. Zhu, Zhipeng, Xu, Jiuhua, Li, Lulu, Zeng, Junjie, Huang, Zhengjie. . Comprehensive analysis reveals CTHRC1, SERPINE1, VCAN and UPK1B as the novel prognostic markers in gastric cancer. In Translational cancer research, 9, 4093-4110. doi:10.21037/tcr-20-211. https://pubmed.ncbi.nlm.nih.gov/35117779/