Downregulation of Annexin A11 (ANXA11) Inhibits Cell Proliferation, Invasion, and Migration via the AKT/GSK-3β Pathway in Gastric Cancer

膜联蛋白 A11 (ANXA11) 下调通过 AKT/GSK-3β 通路抑制胃癌细胞增殖、侵袭和迁移

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作者:Kelei Hua, Yong Li, Qun Zhao, Liqiao Fan, Bibo Tan, Jianbin Gu

Abstract

BACKGROUND Gastric cancer (GC) is one of the most common malignant tumors in the world and in China the incidence and mortality rates of gastric cancer are the second highest among all forms of cancer. Annexin A11 (ANXA11) is a member of the annexins family. Previous studies have shown that ANXA11 participates in many cellular functions and has significant influence on ovarian, breast, liver, and colorectal cancer. However, the expression and biological functions of ANXA11 in GC are still unknown. MATERIAL AND METHODS A total of 63 paired gastric cancer tissues and matched adjacent mucosa were used to measure the ANXA11 levels and its correlation with clinical characteristics. We carried out the biological functions and underlying mechanism study using SGC-7901and AGS cell lines. RESULTS The expression of ANXA11 in cancer tissues was higher than in adjacent mucosa at mRNA and protein levels. In clinicopathological analysis, we found that increased expression of ANXA11 was significantly associated with tumor size, tumor infiltration, local lymph node metastasis, TNM staging, and vascular invasion. Small interfering RNA (siRNA) silencing of ANXA11 inhibits cell proliferation, colony formation, migration, and invasion through the AKT/GSK-3β pathway. CONCLUSIONS ANXA11 plays a critical role in regulating GC proliferation, migration, and invasion via the AKT/GSK-3β pathway, and can potentially be used as a prognostic factor and therapeutic target for gastric cancer patients.

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