KLF8 is a transcription factor that functions as both a repressor and activator of RNA polymerase II-mediated transcription 1. It binds CACCC-box promoter elements and the GT-box of the cyclin D1 promoter, mediating cell cycle progression at G1 phase as a downstream target of focal adhesion kinase (FAK) via the PI3K-Akt-Sp1 signaling pathway 2. KLF8 also directly activates MMP9 transcription, promoting extracellular matrix degradation critical for invasion 3. In cancer progression, KLF8 is frequently overexpressed across multiple tumor types including breast, gastric, pancreatic, ovarian, and lung cancers 456. KLF8 overexpression promotes epithelial-mesenchymal transition (EMT) primarily by repressing E-cadherin transcription while inducing invasive and metastatic phenotypes 36. TGF-β1 activates KLF8 expression through Smad2-mediated promoter binding in ovarian cancer 6. KLF8 knockdown suppresses cell proliferation, induces cell cycle arrest (G1 or G2/M phase), increases apoptosis, and reduces tumor growth in multiple cancer models 145. These findings position KLF8 as a critical oncogenic driver and potential therapeutic target for cancer treatment.