Targeting Cystatin SN Inactivates AKT Pathway to Decrease Cell Proliferation, Migration, and Invasion in Thyroid Cancer

Cystatin SN (CST1) is a cysteine protease inhibitor presenting with multiple biological functions including oncogenesis. This study aimed to explore the effect of CST1 knockdown on cell proliferation, apoptosis, migration, and invasion, and its potential downstream pathways in thyroid cancer. TPC-1 and FTC-133 cell lines were cultured, and were transfected by small interfering RNA targeting CST1 (siCST1) or negative control (siNC), and no transfected control was set. Afterwards, AKT pathway was activated by 740Y-P in combination with siCST1 or siNC transfection in the cells. Cell proliferation, cell migration rate during 24 h, invasive cells were decreased, and cell apoptosis rate was increased after siCST1 transfection compared with siNC transfection in TPC-1 and FTC-133 cells. p-ERK/ERK expression was not different, but p-AKT/AKT expression was downregulated after siCST1 transfection compared with siNC transfection in TPC-1 and FTC-133 cells. By 740Y-P activation of AKT pathway, cell proliferation, cell migration rate during 24 h, invasive cells were elevated after siNC+740Y-P treatment compared with siNC treatment, and were also elevated after siCST1+740Y-P treatment compared with siCST1 treatment in TPC-1 and FTC-133 cells; moreover, cell apoptosis rate showed an opposite trend. CST1 knockdown inactivates AKT pathway to decrease cell proliferation, migration, invasion and increase cell apoptosis rate in thyroid cancer cell lines, indicating a potential target for thyroid cancer.