Friend leukemia virus integration 1 is a predictor of poor prognosis of breast cancer and promotes metastasis and cancer stem cell properties of breast cancer cells

摘要

Breast cancer is the most common cancer in women worldwide; despite the developments in diagnosis and therapy, recurrence and metastasis remain the main causes of death among patients with breast cancer. This study aimed to identify a promising biomarker for this disease. The study clarified (1) the association between Friend leukemia virus integration 1 (FLI‐1) and various molecular subtypes and (2) the prognostic value of FLI‐1 in breast cancer. To the best of our knowledge, this study is the first to report that FLI‐1 is a predictor of poor prognosis in patients with breast cancer and overexpressed in the triple negative breast cancer (TNBC) subtype. To further verify the effect of FLI‐1 in promoting the metastasis of TNBC, we performed a series of functional experiments in vitro and orthotopic xenograft experiments in the mammary fat pad of nude mice. FLI‐1, as a transcription factor, bound to the promoters of key EMT‐related genes (CDH1 and VIM), and regulated their expressions at the transcriptional level, thus induced epithelial‐mesenchymal transition (EMT). The overexpression of FLI‐1 significantly upregulated the expression of mesenchymal markers. After the modulation of FLI‐1, the changes in mammary stem cell markers (ALDH1A1 and CD133) and the capacity to form mammospheres were consistent with those of the EMT‐related markers. The orthotopic xenograft models further confirmed that the attenuation of stem cell traits after silencing FLI‐1 decreased the ability of tumorigenesis. These results indicate that FLI‐1 is a useful predictor of poor prognosis in patients with breast cancer. Furthermore, the preliminary exploration of metastatic mechanism in the patients with TNBC will provide a potential target to treat breast cancer in the near future.