Oleic acid promotes the development of endometrial cancer by up-regulating KLF4 expression

Objective: To investigate the role and possible molecular mechanism of the transcription factor Krüppel-like factor 4 (KLF4) in the biological phenotype of endometrial cancer cells following induction by oleic acid (OA). Materials and Methods: Ishikawa endometrial cancer cells were grown in vitro with different concentrations of oleic acid. Cell proliferation was measured using the Counting Kit-8 (CCK-8) assay. Cell migration and invasion were evaluated by transwell chamber assay and scratch assay, respectively. The mRNA and protein expression levels of KLF4, ERα, Bcl₂, MMP1, MMP9, were evaluated by qRT-PCR and Western blot, respectively. Results: The expression levels of KLF4, ERα, Bcl₂, MMP1 and MMP9 increased significantly (p < 0.05) upon stimulation of the endometrial cancer cells with oleic acid (200 µM), together with the migration and invasion abilities of the cells (p < 0.05). Up-regulation of KLF4 caused the expression of ERα, Bcl₂ and MMP9 to increase significantly (p < 0.05), whereas down-regulation of KLF4 caused the expression of ERα, Bcl₂, MMP1 and MMP9 to significantly decrease (p < 0.05). The increased expression levels of ERα, Bcl₂, MMP1 and MMP9 upon 200 µM oleic acid stimulation were significantly blocked (p < 0.05) by down-regulation of KLF4. Conclusion: oleic acid promotes the expression of ERα, Bcl₂, MMP1 and MMP9 via up-regulation of KLF4, thus resulting in increased migration and invasion abilities of endometrial cancer cells.

OA; KLF4; Endometrial cancer; Migration; Invasion

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