| Background and objective Lung carcinoma becomes the most dangerous cancer with the highest incidence rate and the fastest death rate in the world. The risk of infection of pulmonary disease and even the lung cancer is greatly increased among Chinese, because of the air pollution more and more badly. The relative five-year survival rate now is only 18%, the primary reason give rise to bad prognosis effect of lung cancer patients is the invasion and metastasis of tumor. Resent research data displays that about 80-90% death cases of lung cancer is because of the metastasis of tumor. Therefore, exploring the specific mechanisms of invasion and metastasis of lung cancer and taking appropriate preventive and treatment measures have significant clinical and social significance. The invasion and metastasis of lung cancer is a continuous, gradual, polygenes and multi-step progress. It may involves dysfunction of multiple signaling pathways and variation of structure and function of genes. Latest findings indicate that the co-transcription activator TAZ, which is the substrate target of Hippo signaling pathway, can activate the expression of multiple oncogenes. It plays an important role in invasion and metastasis of tumor,thus it becomes a new target of the anti-cancer drugs and furthermore turn into the hot spot of cancer research. We demonstrate that constantly accumulation of lactic acid have intimate relationship with tumor metastasis in early research, and epithelial- mesenchymal transition as an early event in tumor metastasis may be affected by the accumulation of lactic acid in cells. So we want to find out the relationship between the epithelialmesenchymal transition promoted by TAZ and lactic acid, and deeply interpret the influence in tumor metastasis by TAZ. Epithelial- mesenchymal transition progress regulated by several key transcription factors, early study show that Snail, a transcription factor with the function of regulating marker protein of epithelial cell, play a key role in this progression. So that this research further exploring whether TAZ start the epithelial- mesenchymal transition through Snail or not. This article is aimed at probing the deeply affiliation between lactic acid and epithelial- mesenchymal transition as well as the role of TAZ in this process. Furthermore, illuminating molecular mechanism of tumor metastasis to provide a new target and strategy for oncotherapy.Materials and methods Selecte non-small cell adenocarcinoma H1299 and A549 cell line as research subject. 1、Western blot was used to detected the changes of expression of TAZ and Snail before and after lactate disposition in H1299 and A549 cell lines. 2、After transfection of TAZ si RNA, transfection efficiency and changes of expression of Snail was tested by Western blot. 3、After transfection of TAZ si RNA,TAZ,TAZS89 A, Snail promoter and CMV, changes of expression of Snail was tested by luciferase assay. 4、After transfection TAZ(35)304,TAZ(35)CC,TAZ(35)WW, TAZ, TAZS89 A, transfection efficiency and changes of expression of Snail was tested by Western blot. Results 1、The activity of TAZ rise up and Snail was up regulated after the disposition of lactate. 2、After transfection of TAZ si RNA, the protein level of TAZ decreased and Snail was down regulated. 3、The expression level of Snail increased after transfection of TAZ, TAZS89 A, yet after transfection of TAZ si RNA it is down(H1299:p=0.006,0.001,0.000,A549:p=0.020,0.021,0.017). 4、After transfection of TAZ Snail up regulated except TAZ(35)CC. Conclusions 1、Lactate activate TAZ and Snail in both cell linesand this function has gradient effect. 2、TAZ can induce the expression of Snail. 3、The migration ability of H1299 and A549 cell could be enhanced by TAZ, while delete the CC domain of TAZ the feature is disappeared, and the up-regulatio of Snail also lost. Indicate that CC domain is necessary for TAZ to facilitate EMT. |
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