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