LASP-1 induces proliferation, metastasis and cell cycle arrest at the G2/M phase in gallbladder cancer by down-regulating S100P via the PI3K/AKT pathway

LASP-1 通过 PI3K/AKT 通路下调 S100P,诱导胆囊癌增殖、转移和细胞周期停滞于 G2/M 期

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作者:ZhiZhen Li, YuanYuan Chen, XuAn Wang, HongChen Zhang, Yijian Zhang, YaoHui Gao, Mingzhe Weng, Lei Wang, HaiBin Liang, MaoLan Li, Fei Zhang, Shuai Zhao, Shibo Liu, Yang Cao, Yijun Shu, Runfa Bao, Jian Zhou, Xiyong Liu, Yun Yan, Lei Zhen, Qian Dong, Yingbin Liu

Abstract

LASP-1 is an actin-binding protein that regulates cytoskeletal dynamics and cell migration. LASP-1 was previously identified in a cDNA library from metastatic breast cancer samples. This protein has since been detected in multiple human cancers, including liver cancer, gastric cancer and pancreatic cancer. S100P is a small calcium-binding protein in the S100 protein family that regulates cellular, physiological and pathological processes in various cancers. However, the clinical significance of LASP-1 and S100P expression in gallbladder cancer (GBC) is not yet clear. In our study, we focused on the clinical significance, biological function and mechanism of LASP-1 in gallbladder cancer and detected LASP-1 and S100P overexpression in GBC tissues. The expression of LASP-1 was significantly correlated with poor prognosis in GBC patients (P < 0.05). Furthermore, down-regulation of LASP-1 expression resulted in the obvious inhibition of proliferation and migration and caused cell cycle arrest by down-regulating S100P via the PI3K/AKT pathway; in mice, tumor volume was significantly decreased. In conclusion, LASP-1 may act as an oncogene to regulate the expression of S100P to influence cellular functions in GBC. LASP-1 could serve as a genetic treatment target in GBC patients.

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