Special AT-rich sequence binding protein 1 regulates the multidrug resistance and invasion of human gastric cancer cells

Abstract

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear factor that functions as a global chromatin organizer to regulate gene expression. Recent studies have suggested an oncogenic role of SATB1 in breast cancer. However, the role of SATB1 in gastric cancer, especially in regulating the malignant phenotypes, including multidrug resistance (MDR) and metastasis, remains poorly understood. In this study, the aggressive human gastric cancer cell line SGC7901 and its corresponding MDR variant SGC7901/VCR cells were used as a model. SATB1 expression was examined by RT-PCR and western blot analysis. Results showed that SATB1 was upregulated in SGC7901/VCR cells. An in vitro drug sensitivity assay demonstrated a positive correlation between SATB1 expression levels and drug resistance. Gain and loss of SATB1 function experiments further demonstrated that SATB1 contributes to MDR by inhibiting the accumulation of vincristine (VCR) in gastric cancer cells and protecting the cells from VCR-induced apoptosis. In addition, SATB1 may promote the invasion of gastric cancer cells. The present study provides a novel insight into the oncogenic role of SATB1 in gastric cancer, suggesting that SATB1 is a promising target for the therapy of drug-resistant and invasive gastric cancer.