FBXL16 modulates the proliferation and autophagy in breast cancer cells via activating SRC-3-AKT signaling pathway.

Breast cancer (BC) is the major reason of cancer deaths in females. However, the underlying mechanism remains to be elucidated. F-box and leucine-rich repeat protein 16 (FBXL16) is known to be an important protein in regulating cancer growth. Nonetheless, little is known about FBXL16 in BC. Herein, FBXL16 protein expression was found to be elevated in the tumor tissues of BC patients and BC cell lines (MDA-MB-231, MCF-7, MDA-MB-361, and T47D). FBXL16 silencing inhibited cell growth and increased cell apoptosis as well as cell autophagy in MDA-MB-231 and MCF-7 cells, indicating that FBXL16 could aggravate malignant behaviors in BC. Moreover, FBXL16 deficiency was demonstrated to reduce the level of steroid receptor coactivator 3 (SRC-3) in MDA-MB-231 and MCF-7 cells. FBXL16 silencing also suppressed the level of p-AKT and p-mTOR. Whereas SCR-3 overexpression reversed FBXL16 knockdown-mediated p-AKT and p-mTOR reduction. Rescue assays uncovered that SRC-3 overexpression offset FBXL16 silencing-mediated decrease in cell proliferation and increase in cell apoptosis and autography in MDA-MB-231 and MCF-7 cells. In conclusion, our study found that FBXL16 modulates cell proliferation and autophagy in BC cells via activating the SRC-3-AKT signaling pathway, which shed a light on potential novel biomarkers for the treatment of BC.