Cystatin SN Affects Cell Proliferation by Regulating the ERα/PI3K/AKT/ERα Loopback Pathway in Breast Cancer

Cystatin SN (CST1) has been reported to act as an oncogene in cancers, but its underlying mechanism remains unclear.

We performed Western blotting analyses to observe protein expression and conducted transwell invasion, wound healing, and colony formation assays to assess cell invasion, migration, and proliferation, respectively. We also performed cell cycle analyses by flow cytometry to determine the role of CST1 in the cell cycle. In vivo experiments used subcutaneous tumor models in BALB/c-nu athymic female mice to evaluate the effect of CST1 on tumor growth.

Western blotting analyses showed that CST1 was upregulated in ER+ breast cancer cells such as MCF7, T47D, and BT474. CST1 knockdown led to slower cell growth and inhibited the G1 to S phase transition in ER+ breast cancer cells. In vivo experiments showed that CST1 deletion inhibited tumor growth, and led to decreased expression of estrogen receptor α (ERα) and p-AKT. In vitro experiments showed that the over-expression of CST1 led to the upregulation of ERα, and inhibition of CST1 inhibited the expression of ERα. Western blotting analyses showed that CST1 regulated the activity of the PI3K/AKT signaling pathway in breast cancer cells. We confirmed that CST1 acted as an oncogene in ER+ breast cancer by regulating the ERα/PI3K/AKT/ERα loopback pathway.

CST1 acts as an oncogene in ER+ breast cancer, and CST1 contributes to cancer development by regulating the ERα/PI3K/AKT/ERα loopback pathway in ER+ breast cancer. Our findings indicate that CST1 could be a significant therapeutic target for ER+ breast cancer patients. Our discovery should inspire further studies on the role of CST1 in cancers.