Slc14a1, also known as the gene encoding the type-B urea transporter (UT-B), facilitates the passive movement of urea across the cell membrane, playing a role in urinary concentration and urea nitrogen recycling in the kidney [2,4]. It has been associated with multiple biological processes and disease-related pathways.

In cancer research, in bladder cancer, interferon-dependent SLC14A1+ cancer-associated fibroblasts promote cancer stemness via the WNT5A paracrine pathway, and inhibition of their formation can sensitize tumor cells to chemotherapy [1]. In colorectal cancer, SLC14A1 is a key regulator in metachronous liver metastasis, interacting with TβRII to amplify TGF-β/Smad signaling, and a positive feedback loop exists between SLC14A1 and TGF-β1 [3]. In renal cancer, low expression of SLC14A1 is associated with a better prognosis, and upregulation of its expression inhibits cancer cell proliferation, invasion, and metastasis [4]. In urothelial carcinoma, SLC14A1 acts as a tumor suppressor, preventing oncometabolite accumulation and transrepressing oncometabolite genes [5]. In prostate cancer, down-regulation of SLC14A1 activates CDK1/CCNB1 and mTOR pathways, promoting tumor progression [6]. In non-small cell lung cancer, low expression of SLC14A1 indicates poor prognosis and promotes cell proliferation and migration [7].

In conclusion, Slc14a1 has diverse functions in the body, especially in maintaining urea transport-related physiological processes. In the context of cancer, studies, though not specifically from KO/CKO mouse models in the given references, suggest that Slc14a1 can play either tumor-promoting or tumor-suppressive roles depending on the cancer type, highlighting its potential as a biomarker and therapeutic target in various cancers.