Abstract P2-01-22: KLF4 improve prognosis of triple negative breast cancer by suppression of epitherial mesenchymal transition

Abstract

Abstract Background Triple negative breast cancer (TNBC) is highly malignant and prone to metastasis and relapse, and therefore has poorer prognosis than other sub-types. The mechanism of higher malignancy of TNBC has not been sufficiently elucidated. KLF4is reported to be a transcription factor that is associated with both tumor suppression and oncogenesis. We have reported that breast cancer patients with strong expression of KLF4 had better prognosis, especially in TNBC patients. And here we report that KLF4 negatively regulates the metastasis and growth of TNBC. Methods We assessed the expression levels of KLF4 in 84 patients with TNBC by immunohistochemical staining and studied the patterns of metastasis/recurrence clinicopathologically. The overall survival (OS) rate and the disease free survival (DFS) rate after surgery was calculated by Kaplan-Maier method. In addition, circulating tumor cells (CTCs) in the peripheral blood of TNBC patients were identified and compared with primary lesions in terms of KLF4 expression. Moreover, the expression of KLF4 was inhibited by transfecting cultured TNBC cells (MDA-MB231) with the small interfering RNA (siRNA) of KLF4 to analyze the effects of KLF4 on cell proliferation and epithelial-mesenchymal transition (EMT)-like changes. For the proliferation assay, measurements were made by MTT assays. Cell migration and invasion assays of KLF4 suppressed TNBC cells were also examined. Total RNA was extracted from these cells, cDNA was synthesized, and used for the quantitative polymerase chain reaction (qPCR) analysis. Results In the 84 TNBC patients, higher KLF4 expression was associated with significantly better OS and DFS. An analysis of KLF4 expression in CTCs of the TNBC patients showed that KLF4 expression was lower in CTCs than in primary cancer lesions. TNBC cells (MDA-MB231) that were transfected the KLF4 siRNA exhibited a greater ability to growth than controls. These cells also underwent EMT-like changes with reduced expression of epithelial factors such as E-cadherin. Treating these TNBC cells with eribulin resulted a reduction of the expression of stem cell/EMT markers. Conclusion TNBC patients with reduced KLF4 expression had poor outcomes. The results of our experiments suggest the expression of KLF4 is one of the important factors that inhibit the EMT and growth of TNBC. Citation Format: Nagata T, Sekine S, Arai M, Fujii T. KLF4 improve prognosis of triple negative breast cancer by suppression of epitherial mesenchymal transition [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-22.