CLDN11 deficiency upregulates FOXM1 to facilitate breast tumor progression through hedgehog signaling pathway

IF 2.9 4区生物学 Q3 CELL BIOLOGY Journal of Molecular Histology Pub Date : 2024-10-22 DOI:10.1007/s10735-024-10267-5

Leyi Yang, Xiaoping Wang, Qinghai Lin, Guoyi Shen, Hong Chen

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Abstract

Claudins (CLDNs) play a crucial role in regulating the permeability of epithelial barriers and can impact tumor behavior through alterations in their expression. However, the precise mechanisms underlying the involvement of CLDNs in breast cancer progression remain unclear. This study aimed to investigate the role of CLDN11 in breast cancer progression. Utilizing the TCGA database and clinical specimens from breast cancer patients, we observed reduced expression of CLDN11 in tumor tissues, which correlated with poor prognosis in breast cancer patients. In vitro, silencing of CLDN11 enhanced the proliferative and migratory characteristics of breast cancer cell lines MCF-7 and MDA-MB-231. Mechanistically, CLDN11 deficiency promoted the upregulation of Forkhead Box M1 (FOXM1) by activating the hedgehog signaling pathway, thereby sustaining tumor progression in breast cancer. In vivo, blockade of hedgehog signaling suppressed the tumor progression induced by CLDN11 silencing. Our study highlights the significance of the CLDN11/FOXM1 axis in breast cancer progression, suggesting CLDN11 as a potential diagnostic indicator and therapeutic target for clinical therapy.

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CLDN11 缺乏会上调 FOXM1，通过刺猬信号通路促进乳腺肿瘤的进展。

克劳蛋白（CLDNs）在调节上皮屏障的通透性方面发挥着至关重要的作用，并可通过改变其表达影响肿瘤行为。然而，CLDNs参与乳腺癌进展的确切机制仍不清楚。本研究旨在探讨CLDN11在乳腺癌进展中的作用。利用 TCGA 数据库和乳腺癌患者的临床标本，我们观察到 CLDN11 在肿瘤组织中的表达减少，这与乳腺癌患者的不良预后相关。在体外，沉默 CLDN11 会增强乳腺癌细胞株 MCF-7 和 MDA-MB-231 的增殖和迁移特性。从机理上讲，CLDN11的缺乏会通过激活刺猬信号通路促进叉头盒M1（FOXM1）的上调，从而维持乳腺癌的肿瘤进展。在体内，阻断刺猬信号抑制了CLDN11沉默诱导的肿瘤进展。我们的研究强调了CLDN11/FOXM1轴在乳腺癌进展中的重要作用，提示CLDN11是一种潜在的诊断指标和临床治疗靶点。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.