FBXL10对ERRα的调控及在乳腺癌细胞能量代谢过程中的作用机制

Breast cancer is the most common female malignant tumor. The main death of the patients are mainly caused by vigorous metabolism, malignant proliferation and metastasis of cancer cells. It is important for the prevention and treatment of breast cancer to reveal the roles which related genes and proteins played in the process of cell energy metabolism and signal network. Based on the clinical sample analysis, the expression of ERRα (estrogen receptor related receptor α) and ME1 (malic enzyme) which is the glycolysis and the Krebs cycle oxidative phosphorylation of metabolic enzymes showed a positive correction. The limited study showed that ERRα takes the crucial effect in cell energy metabolism. Our preliminary data showed that FBXL10 (histone demethylase) could interact with ERRα, suggesting that FBXL10 may play roles in the process of the cell energy metabolism mediated by ME1 through regulating ERRα, however, the specific molecular mechanism needs to be further studied. Our project will discuss the mechanism of the related factors in regulating the energy metabolism of breast cancer cells via molecular and cell biology method such as gene knock-down or overexpression in combination with enzyme activity measurement in vivo or in vitro, along with the animal models and clinical samples, and our research will supply the new idea for the prevention and treatment of breast cancer as well as the novel targets for the drug discovery.

乳腺癌是女性最常见的恶性肿瘤，肿瘤细胞代谢旺盛、恶性增殖与转移是患者死亡的主要原因。揭示相关基因、蛋白在细胞能量代谢过程中的作用及信号网络是乳腺癌防治研究的重要课题。基于临床样本表达水平的分析：雌激素受体相关受体ERRα与苹果酸酶ME1（糖酵解和三羧酸循环氧化磷酸化的代谢酶）呈正相关，有限的研究结果提示ERRα在细胞能量代谢中起重要作用。前期研究结果表明：组蛋白去甲基化酶FBXL10与ERRα具有相互作用，预示FBXL10可能通过调控ERRα，进而在ME1介导的乳腺癌细胞能量代谢过程中发挥作用，具体的分子机制有待进一步探讨。本项目拟利用基因敲低或过表达，结合体内、外酶活性测定等分子与细胞生物学手段，以及动物模型和临床样本，研究这些因子在乳腺癌细胞能量代谢过程中的作用机制，为乳腺癌的防治提供思路，为新药研发提供靶标。

乳腺癌是女性最常见的恶性肿瘤，肿瘤细胞代谢旺盛、恶性增殖与转移是患者死亡的主要原因。揭示相关基因、蛋白在细胞能量代谢过程中的作用及信号网络是乳腺癌防治研究的重要课题。基于临床样本表达水平的分析：雌激素受体相关受体ERRα与苹果酸酶ME1（糖酵解和三羧酸循环氧化磷酸化的代谢酶）呈正相关，有限的研究结果提示ERRα在细胞能量代谢中起重要作用。前期研究结果表明：组蛋白去甲基化酶FBXL10与ERRα具有相互作用，预示FBXL10可能通过调控ERRα，进而在ME1介导的乳腺癌细胞能量代谢过程中发挥作用，具体的分子机制有待进一步探讨。本项目拟利用基因敲低或过表达，结合体内、外酶活性测定等分子与细胞生物学手段，以及动物模型和临床样本，研究这些因子在乳腺癌细胞能量代谢过程中的作用机制，为乳腺癌的防治提供思路，为新药研发提供靶标。