Claudins (CLDNs) are essential for cell adhesion and also play roles in intracellular signaling, regulating processes such as cell proliferation and migration. Although CLDN-mediated signaling can influence cancer progression, the mechanisms are poorly understood. Among them, CLDN10 is known to be downregulated at the mRNA level in renal cell carcinoma (RCC) and may serve as a prognostic marker, but its protein-level function remains unclear. This study aimed to investigate the clinical significance of CLDN10 expression in clear cell renal cell carcinoma (ccRCC) and its role in promoting cancer progression.

A novel monoclonal antibody (mAb) was developed to specifically recognize CLDN10. Using this mAb, we performed immunohistochemical analysis on tumor samples from 165 ccRCC patients treated at Fukusima Medical University between 2002 and 2020. CLDN10 expression levels were semiquantitatively scored and correlated with clinicopathological features and survival outcomes. ccRCC cell lines (786-O, ACHN, OS-RC-2) were engineered to overexpress CLDN10, and functional assays including MTT, BrdU incorporation, and wound healing were conducted. To identify CLDN10-binding partners, immunoprecipitation followed by mass spectrometry (IP-MS) was performed. Identified interactors were validated by co-immunoprecipitation, immunofluorescence, and loss-of-function studies.

High CLDN10 expression was significantly associated with TNM stage III/IV (p = 0.034), WHO grade 3/4 (p < 0.001), and venous invasion (p = 0.023). Kaplan–Meier analysis showed that high CLDN10 expression was significantly associated with poorer cancer-specific survival (p = 0.0029), and multivariate analysis confirmed it as an independent prognostic factor (HR = 3.623, 95% CI = 1.121–10.752). In ccRCC cells, CLDN10 overexpression enhanced cell viability, proliferation, and migration. Transcriptome analysis revealed activation of the mTOR pathway and upregulation of MYC target genes. IP-MS identified LAT1 (SLC7A5), an amino acid transporter, as a CLDN10-interacting protein. Co-localization at the plasma membrane was confirmed by immunofluorescence. Functional assays demonstrated that CLDN10 promoted amino acid uptake in a LAT1-dependent manner. Knockdown of LAT1 abolished the oncogenic effects induced by CLDN10 overexpression.

CLDN10 promotes ccRCC progression by forming a functional complex with LAT1, enhancing amino acid transport and activating oncogenic pathways including mTOR and MYC. These findings suggest that the CLDN10–LAT1 axis may serve as a novel therapeutic target in ccRCC. Our results also highlight the broader role of CLDNs in cancer signaling, where their function is shaped by specific interacting partners.