Research on the Expression and Clinical Significance of KLF4 and KLF5 in Breast Cancer

³ Department of Pathology, Baoding NO.1 Central Hospital, Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province, Baoding 071000, Hebei, China,

PAR 2025 , 9(6), 119–125; https://doi.org/10.26689/par.v9i6.13025

© 2025 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

As members of the Kruppel-like transcription factor family, KLF4 and KLF5 play critical roles in the development and progression of breast cancer, yet their functions are complex. KLF4 exhibits a dual role: on one hand, it inhibits metastasis by suppressing epithelial-mesenchymal transition (EMT) and activating E-cadherin transcription; on the other hand, it can sustain tumor stem cell properties to promote progression. Its tumor-suppressive or tumor-promoting effects are highly dependent on the status of p21 and the cellular microenvironment. KLF5 is significantly overexpressed in basal-like breast cancer (BLBC) and triple-negative breast cancer (TNBC), promoting tumor proliferation and metastasis by regulating the cell cycle (inducing Cyclin D1 and inhibiting p27), maintaining stemness (activating Slug/Nanog), and forming a positive feedback loop with KLF5-XPO1. Clinical studies have demonstrated that overexpression of KLF4 is associated with poor prognosis in patients, while small-molecule inhibitors targeting KLF5 (such as mifepristone and CDK7/BRD4 inhibitors) can inhibit the growth of triple-negative breast cancer (TNBC). Both KLF4 and KLF5 influence breast cancer heterogeneity and treatment response by regulating key signaling pathways. Future research should further elucidate their environment-dependent mechanisms to develop precise targeting strategies.

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