Expression of the β3 subunit of Na(+)/K(+)-ATPase is increased in gastric cancer and regulates gastric cancer cell progression and prognosis via the PI3/AKT pathway.
Expression of the β3 subunit of Na(+)/K(+)-ATPase is increased in gastric cancer and regulates gastric cancer cell progression and prognosis via the PI3/AKT pathway.
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Na /K -ATPase β 3 亚基在胃癌中表达增加，并通过 PI3/AKT 通路调节胃癌细胞进展和预后
DOI：
10.18632/oncotarget.20894
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发表时间：
2017-10-13
期刊：
影响因子：
--
通讯作者：
Fei S
中科院分区：
文献类型：
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作者：
Li L;Feng R;Xu Q;Zhang F;Liu T;Cao J;Fei S
ATP 1B 3编码Na+/K+-ATP酶的β3亚基，位于3号染色体q22-23区域。Na+/K+-ATP酶参与正常的细胞活动，但在肿瘤发生中也起着至关重要的作用。在本研究中，我们发现Na+/K+-ATP酶β3亚基在人胃癌组织中的表达比正常对照组织中的表达增加，并且这种增加的表达预示着不良的预后。与正常胃上皮细胞系相比，胃癌细胞系中ATP 1B 3的表达在mRNA和蛋白水平上均升高。有趣的是，ATP 1B 3敲低显著抑制人胃癌细胞系的细胞增殖、集落形成能力、迁移和侵袭，并增加凋亡。此外，敲低诱导细胞周期停滞在G2/M期。此外，我们证明ATP 1B 3沉默降低了磷脂酰肌醇3-激酶（PI 3 K）、蛋白激酶B（AKT）和磷酸化AKT（p-AKT）的表达，表明ATP 1B 3通过PI 3 K/AKT信号通路调节胃癌细胞的进展。因此，Na+/K+-ATP酶β3亚基在胃癌的发生发展中起重要作用，并可能成为胃癌预后和治疗的潜在靶点。
ATP1B3 encodes the β3 subunit of Na+/K+-ATPase and is located in the q22-23 region of chromosome 3. Na+/K+-ATPase participates in normal cellular activities but also plays a crucial role in carcinogenesis. In the present study, we found that expression of the β3 subunit of Na+/K+-ATPase was increased in human gastric cancer tissues compared with that in normal matched tissues and that this increased expression predicted a poor outcome. ATP1B3 expression was elevated at both the mRNA and protein levels in gastric cancer cell lines relative to those in a normal gastric epithelial cell line. Interestingly, ATP1B3 knockdown significantly inhibited cell proliferation, colony-formation ability, migration, and invasion and increased apoptosis in human gastric carcinoma cell lines. Additionally, knockdown induced cell cycle arrest at the G2/M phase. Furthermore, we demonstrated that ATP1B3 silencing decreased the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and phosphorylated AKT (p-AKT), indicating that ATP1B3 regulates gastric cancer cell progression via the PI3K/AKT signalling pathway. Hence, the β3 subunit of Na+/K+-ATPase plays an essential role in the tumourigenesis of gastric cancer and may be a potential prognostic and therapeutic target for the treatment of gastric cancer.