CST1 Promotes Cancer Cell Progression By Regulating The ERα/PI3K/Akt/ERα Loopback Pathway In Breast Cancer

Purpose:Cystatin SN(CST1)is upregulated in various tumors,and its high expression contributes to tumor recurrence,metastasis,and poor survival outcomes.Although CST1 has been widely studied in tumors,its role in estrogen receptor-positive(ER~+)breast cancer was never clearly studied.This study aimed to investigate the effects of CST1 on cell proliferation,cell invasion and migration in ER~+breast cancer cells,reveal the regulation of CST1 on estrogen receptorα(ERα)and the PI3K/Akt signaling pathway,and to uncover the regulation of CST1 on the ERα/PI3K/Akt/ERαloopback pathway.Methods:This subject was based on ER~+breast cancer cell lines MCF7,T47D and BT474.Si RNA transfection technology was used to knock down the expression of CST1 in ER~+breast cancer cells.Colony formation experiments,transwell experiments,scratch experiments,and flow cytometry were used to detect the effects of CST1knockdown on cell growth,invasion,migration,cell cycle in ER~+breast cancer cells.The expression of proteins was detected by Western blotting.The CST1 stably knockdown cell line MCF7 sh CST1 was constructed by lentiviral packaging method.The tumor model was established by subcutaneous injection of the cells into female nude mice.In vivo experiment was conducted to analyze the effect of CST1 on tumor growth in ER~+breast cancer.The effect of CST1 on ERαubiquitination was explored by ubiquitination experiments.Results:(1)CST1 expression is significantly up-regulated in ER~+breast cancer cells.(2)CST1 knockdown inhibits cell proliferation,invasion and migration,and inhibits cell cycle in ER~+breast cancer cells.(3)In vivo experiments show that knockdown of CST1 significantly inhibited the tumor growth.(4)CST1 regulates the expression of ERαand the PI3K/Akt signaling pathway.(5)A mutual regulation existed between ERαand PI3K/Akt signaling pathway in ER~+breast cancer cells.(6)CST1 knockdown contributes to ERαubiquitination and degradation.Conclusions:CST1 affects cell proliferation and promotes tumor growth by regulating the ERα/PI3K/Akt/ERαloopback pathway in ER~+breast cancer cells.CST1 might serve as a potential target for the treatment of ER~+breast cancer.