Claudin proteins are a major component of the tight junctions between cells, which are involved in a variety of human diseases, including
cancer. This study aimed to investigate the functional role of
claudin 19 (CLDN19) in human
breast cancer progression. Here, we firstly found that CLDN19 was downregulated in
breast tumor tissues than normal control, and loss of CLDN19 predicted poor patient survival in patients with
breast cancer, by utilizing the
Cancer Genome Atlas Program (TCGA) dataset analysis. To further validate the
tumor suppressive effects of CLDN19, we established CLDN19 overexpressed MDA-MB-231 and T47D cells. And overexpression of CLDN19 resulted in suppression of cell growth/migration in
breast cancer cells cultured in 3D environment or in vivo. Mechanistically, we demonstrated that CLDN19 downregulated
ubiquitin conjugating enzyme E2 C (UBE2C) expression, which further suppressed Wnt/β-
catenin pro-survival signaling pathway activation induced by extracellular matrix (ECM), in 3D environment or in vivo. Altogether, our study revealed a
tumor suppressive role of CLDN19, which hindered ECM/UBE2C/Wnt signaling activation in
breast cancer, and offered novel insight for
tumor diagnosis and targeted
therapy.