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新型黏着斑蛋白 kindlin-2 通过整合素 β1 和 β3 的磷酸化促进胃癌细胞的侵袭。

Novel focal adhesion protein kindlin-2 promotes the invasion of gastric cancer cells through phosphorylation of integrin β1 and β3.

机构信息

Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, PR China.

出版信息

J Surg Oncol. 2013 Aug;108(2):106-12. doi: 10.1002/jso.23353.

DOI:10.1002/jso.23353
PMID:23857544
Abstract

BACKGROUND

We have found that the expression of the novel focal adhesion protein kindlin-2 had a significant positive correlation with poor survival in gastric cancer. However, the mechanism by which kindlin-2 acts in gastric cancer warrants further evaluation.

METHODS

Kindlin-2 mRNA expression in gastric cancer cell lines was measured by realtime RT-PCR under normal and hypoxic conditions. Cell proliferation, apoptosis, cell cycle, tumor adhesion, cell invasion ability, and phosphorylation of integrin β1 and β3 proteins were measured to assess the influence of kindlin-2 on the malignant behavior of gastric cancer cells.

RESULTS

Kindlin-2 mRNA expression was highest in the distant metastasis gastric cancer cell line Hs-746T. Cell proliferation, adhesion with endothelium and collagen IV, invasion rate, and angiogenesis genes expression, as well as phosphorylation of integrin β1 and β3 in Hs-746T, were decreased significantly after kindlin-2 downregulation, but there was no change in apoptosis and cell cycle.

CONCLUSIONS

Kindlin-2 might promote the invasion of gastric cancer cells through enhancing proliferation and adhesion by the phosphorylation of integrin β1 and β3.

摘要

背景

我们发现 novel focal adhesion protein kindlin-2 的表达与胃癌患者的不良预后有显著的正相关。然而,kindlin-2 在胃癌中的作用机制仍需要进一步评估。

方法

实时 RT-PCR 检测正常和低氧条件下胃癌细胞系中 kindlin-2 mRNA 的表达。检测细胞增殖、凋亡、细胞周期、肿瘤黏附、细胞侵袭能力以及整合素 β1 和 β3 蛋白的磷酸化,以评估 kindlin-2 对胃癌细胞恶性行为的影响。

结果

kindlin-2 mRNA 在远处转移胃癌细胞系 Hs-746T 中表达最高。下调 kindlin-2 后,Hs-746T 细胞的增殖、与内皮细胞和胶原 IV 的黏附、侵袭率以及血管生成基因的表达,以及整合素 β1 和 β3 的磷酸化均显著降低,但凋亡和细胞周期无变化。

结论

kindlin-2 可能通过整合素 β1 和 β3 的磷酸化增强增殖和黏附来促进胃癌细胞的侵袭。

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