Overexpression of Aquaporin-1 Promotes Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties via Wnt/β-Catenin Signaling Pathway in Advanced Breast Cancer Cells.

IF 3 2区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Carcinogenesis Pub Date : 2025-07-09 DOI:10.1002/mc.70009

Shan Wu, Haiyan Hu, Xiuhong Wang, Zhan Hua, Jianjun Zhou

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引用次数: 0

Abstract

Tumor metastasis and the persistence of cancer stem cells (CSCs) are the main factors contributing to tumor malignancy, particularly in breast cancer. Uncovering the critical molecular mechanisms and therapeutic targets is essential for addressing this challenge. The present study revealed that aquaporin-1 (AQP1) was highly expressed in breast cancer and was closely associated with poor patient prognosis. AQP1 overexpression significantly enhanced multiple cellular processes in breast cancer cells, including cell proliferation, migration, invasion, spheroid formation, and three-dimensional (3D) spheroid invasion. Moreover, AQP1 activated the Wnt/β-catenin signaling pathway, and promoted the expression of epithelial-mesenchymal transition (EMT)-related markers (N-cadherin and vimentin) and CSC markers (SOX2 and c-Myc). Furthermore, small hairpin (sh)RNA-mediated downregulation of β-catenin confirmed the mechanism by which AQP1 promoted EMT and CSC properties through the activation of the Wnt/β-catenin signaling pathway. In conclusion, the present study elucidated the molecular mechanism through which AQP1 advanced breast cancer progression via the Wnt/β-catenin signaling pathway, providing insights into the mechanisms underlying breast cancer progression and offering valuable implications for developing novel therapeutic strategies.

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水通道蛋白-1的过表达通过Wnt/β-Catenin信号通路促进晚期乳腺癌细胞上皮-间质转化和癌症干细胞特性

肿瘤转移和肿瘤干细胞（CSCs）的持续存在是导致肿瘤恶性的主要因素，尤其是乳腺癌。揭示关键的分子机制和治疗靶点对于解决这一挑战至关重要。本研究发现水通道蛋白-1 （AQP1）在乳腺癌中高表达，与患者预后不良密切相关。AQP1过表达显著增强了乳腺癌细胞的增殖、迁移、侵袭、球体形成和三维球体侵袭等多个细胞过程。AQP1激活Wnt/β-catenin信号通路，促进上皮-间质转化（epithelial-mesenchymal transition， EMT）相关标志物（N-cadherin和vimentin）和CSC标志物（SOX2和c-Myc）的表达。此外，小发夹（sh） rna介导的β-catenin下调证实了AQP1通过激活Wnt/β-catenin信号通路促进EMT和CSC特性的机制。总之，本研究阐明了AQP1通过Wnt/β-catenin信号通路促进乳腺癌进展的分子机制，为了解乳腺癌进展的机制提供了新的见解，并为开发新的治疗策略提供了有价值的意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Carcinogenesis 医学-生化与分子生物学

CiteScore

7.30

自引率

2.20%

发文量

112

审稿时长

2 months

期刊介绍： Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.