Na,K-ATPaseβ1亚基在TGF-β诱导的肺癌EMT中的作用及其调节机制

批准号:
81402414
项目类别:
青年科学基金项目
资助金额:
23.0 万元
负责人:
李军霞
依托单位:
学科分类:
H1809.肿瘤复发与转移
结题年份:
2017
批准年份:
2014
项目状态:
已结题
项目参与者:
郭芳、王娜、于丁、王慧慈、候晓敏、张晓飞
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中文摘要
Na,K-ATPase β1亚基作为一种细胞黏附分子可和E-钙粘蛋白结合,共同维持细胞间的紧密连接,在低分化高侵袭的肿瘤,其表达明显降低,且降低程度越低,患者死亡率越高,提示β1亚基与肿瘤转移密切相关,但其下调机制及参与肿瘤转移的途径尚不清楚。上皮间质转化(EMT)是肿瘤转移的重要机制,E-钙粘蛋白下调是EMT的特征之一,肿瘤中β1亚基表达和Snail表达呈反比关系,Snail是转化生长因子(TGF)-β诱导EMT通路中的转录因子,这提示β1亚基可能与TGF-β诱导的EMT有关。我们前期研究发现TGF-β可下调人肺癌A549细胞β1亚基的表达,且基因敲除β1亚基可诱导细胞出现EMT样的形态变化。本研究拟在A549细胞上探讨Na,K-ATPase β1亚基在TGF-β诱导EMT中的作用及其下调机制。研究结果将明确β1亚基的下调机制和参与肿瘤转移的途径,为肿瘤转移的防治提供新的理论及靶点。
英文摘要
Na,K-ATPase β1 subunit is a kind of cell adhesion molecule, and can maintain the intercellular tight junction together with E-cadherin. The expression of Na,K-ATPase β1 subunit was downregulated in poorly differentiated and highly invasive tumors, and the cancer patients with low Na,K-ATPase β1 had a high risk of death,which indicated that β1 subunit was involved in tumor metastasis. The mechanism and role of the Na,K-ATPase β1 downregulation in cancer cells aren’t clear. The downregulation of E-cadherin expression is one sign of epithelial-mesenchymal transition(EMT). The expression of Na,K-ATPase β1 subunit was inversely proportional to the expression of Snail in cancer cells and Snail is a kind of transcription factor involved in transforming growth factor-β(TGF-β)-induced EMT. All these indicated that Na,K-ATPase β1 may be involved in EMT induced by TGF-β. TGF-β signaling contributes to tumor progression by inducing EMT, thereby promoting the conversion of epithelial tumors to invasive, metastatic tumors. We also have shown that TGF-β downregulated the expression of Na,K-ATPase β1 subunit in human lung A549 cancer cells and the cells showed EMT-like morphology after Na,K-ATPase β1 knockout. This project is designed to investigate the role and regulatory mechanism of Na,K-ATPase β1 in EMT induced by TGF-β. This study will increase our knowledge about mechanisms involved in EMT induced by TGF-β and role of Na,K-ATPase β1 in the tumor metastasis. It will provide new thinking and target for treatment of tumor metastasis and add information for the Na,K-ATPase β1 research.
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