肿瘤细胞能量代谢重编程导致糖酵解增强而使大量葡萄糖分解成乳酸。在此过程中，通过上调低氧诱导因子（HIF）来诱导葡萄糖转运体和乳酸转运体的表达，强化葡萄糖摄入以适应其高增殖与转移活性所需能量供给和乳酸的胞外排出而防止酸性引起的细胞凋亡。排出胞外的乳酸是造就肿瘤酸性微环境的主要成分。在前一课题中我们发现，酸性可诱导脂质-质子双配体受体TDAG8的表达，而TDAG8通过诱导乳酸转运体和CD147来提高肿瘤生存率和转移活性。继而又发现TDAG8可上调HIF和葡萄糖转运体。我们认为TDAG8参与肿瘤细胞适应低氧酸性环境的最关键蛋白-HIF的表达。所以，在本课题中，以TDAG8转基因肝癌和肺癌细胞作模型，重点研究TDAG8在酸性（质子）条件下诱导HIF的信号机制和肿瘤代谢关键环节中的调控作用及其代谢机理。为肿瘤治疗中尚未突破的酸性“屏障”（药物抵抗与淋巴细胞凋亡）的攻克研究中指出新的靶位点。

The reprogrammed energy metabolism in tumor cell leads to large amount of glucose breakdown into lactic acid because of increased glycolysis. The tumor cells need to strengthen glucose intake to adopt energy supply for the high proliferation, metastasis and the extracellular excretion of lactic acid to prevent the apoptosis from acidosis through increased expression of glucose transporter and lactic acid transporter. It induced by HIF during this process. The lactic acid excreted from the cell contributes to make an acidic micro-environment outside of the tumor cell. Our previous studies found that acidic condition induced the expression of proton-sensing receptor TDAG8 and TDAG8 further induced the expression of lactic acid transporter and CD147 to improve cancer survival and transfer activity. We also found that TDAG8 up- regulated HIF and glucose transporter. So，it is considered that TDAG8 receptor is involved in tumor cells to adapt to the low oxygen and acidic environment through induction of the most key protein - HIF expression. In this study, we plan to clarify the signaling mechanism of TDAG8 induced HIF expression and its regulatory role in the Key processes of tumor Metabolism in Acidic micro-environment. TDAG8 transgenic hepatocellular （carcinoma）cells and lung cancer cells were used as models in the study. Our research would provide a novel therapeutic target for cancer treatment which focusing on tumor acidic environment（acidic barrier），the unsolved problem in drug resistance and lymphocyte apoptosis.