Claudin 19 inhibits the malignant potential of breast cancer cells by modulating extracellular matrix-associated UBE2C/Wnt signaling.

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. AJCR Copyright © 2022.

Citation

Jingxiu Xu, Mingjie Chen, Mingyu Hu, Hanlu Wang, Zhongqiang Zuo, Jianguo Wang, Zhiyin Xie. Claudin 19 inhibits the malignant potential of breast cancer cells by modulating extracellular matrix-associated UBE2C/Wnt signaling. American journal of cancer research. 2022;12(12):5552-5563

PMID: 36628278

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