3、能量代谢如何决定细胞的命运。近些年来，科学家们逐渐意识到几乎所有的细胞信号转导途径最终都汇集在代谢网络上，这迅速催热了癌症的代谢研究。细胞的代谢是如何决定细胞命运的？是如何决定细胞的转化的？我们的研究将着重理清癌细胞中糖代谢、脂代谢及蛋白质代谢之间的关系，寻找癌细胞得以转化的物质基础(代谢本质)。

4、开发实时生物学功能监测工具。我们将致力于确定研究细胞代谢(决定细胞命运)的方法；将致力于开发实时监测代谢平衡及细胞凋亡的工具。

　　Research Description

　　In the past decades, most researchers working on cancer were focusing on cell signal transduction, and they made profound progress in understanding and treating cancers. However, cancer still remains a medical challenge and numerous questions remain to be explored. Metabolic and signal systems in cancer cells can be driven by each other, and they are closely connected but remain relatively independent. Altering the signal transduction network absolutely will drive corresponding metabolic changes, however, most researchers usually complete their studies without investigating metabolic changes, because under these conditions the signal transduction system is positive and it promotes the passive metabolism. On the other hand, when we perturb the metabolic network by targeting metabolic enzymes or changing their substrates concentrations, the signal system also will change. In this setting, the positive metabolic system drives passive signal transduction, nonetheless, we can not always figure out how cancer cells die by the rules of typical signal transduction. The metabolic system probably has its own ways to induce cell death.

　　Based on our previous studies, we put forward the hypothesis that the irreversible upsetting of metabolic homeostasis can kill cells by some special mechanisms. Cancer cells have many specifically metabolic characteristics that could be rendered as ideal targets for the treatment of cancer. Our future research will be carried out around this hypothesis, and we plan to identify targets to disrupt metabolic homeostasis to kill cancer cells and then dissect their mechanisms.

　　Project I: Role of Rb in controlling cell proliferation, growth and transformation via regulating redox balance. We want to know how Rb controls cellular stress, and how Rb regulation of cell proliferation, growth and transformation is related to its ability to control cellular stress. In Rb mutant cancer cells, how is Rb inactivation-induced lethal redox imbalance suppressed? This research will help to design strategies to treat cancers holding inactivated Rb.

　　Project II: Why do cancer cells need to express high level of FAS and how does FAS inhibition kill cancer cells? We will determine the role of FAS hyperactivity in cancer cells, and dissect the mechanism underlying FAS inhibition-induced cell death. Since targeting FAS has been reported to specifically kill cancer cells, many researchers from all over the world are trying to decipher the detailed mechanism but have failed to do so. It seems that it is not possible to explain FAS action in cancer cells by traditional cell signal transduction. We believe the answer will be found in select metabolic pathways that are critical for cancer cell homeostasis. This study is supposed to provide more targets either alone or together with FAS for the treatment of cancers.

　　Project III: Irreversibly disrupting metabolic homeostasis specifically kills cancer cells. We will determine if metabolic pathways and constituent enzymes play essential roles in maintaining glucose, protein and lipid metabolic homeostasis, and whether they are potential therapeutic targets of cancer cells alone or in combination. We will then dissect the mechanisms by which disruption of metabolic homeostasis leads to cell death. We will set up a highthrough-put screening platform to identify the inhibitors of these pathways/enzymes.

　　Project IV：Development of novel real-time measuring tools and new biotechnologies. We are trying to set up the research platforms for cancer metabolism and make real-time supervising tools/methods for the biological pathways.

　　Selected Publications

1、Tian W., Ma X., Zhang S., Sun Y. and Li B. Fatty Acid Synthase Inhibitors from Plants and Their Potential Application in the prevention of Metabolic Syndrome. Clin Oncol Cancer Res., 8: 1-9. (2011)

2、Li B., Zhao J., Wang CZ, Searle J., He TC., Yuan CS., and Du W. Ginsenoside Rh2 induce apoptosis and paraptosis-like cell death in colon cancer cells through activation p53. Cancer Letters, 28;301(2):185-92. (2011)

3、Li B., Gordon GM., Du CH., Xu J, and Du W. Specific killing of Rb mutant cancer cells by inactivating TSC2. Cancer Cell, 17: 469-480. (2010)

　　Highlighted in Science(328: 1455, 2010)

　　Comments in Cancer Research (70:5198, 2010)

　　Evaluated in“F1000” by“Faculty Of 1000 Biology”.

4、Li B., wang CZ., He TC., Yuan CS., and Du W. Antioxidants potentiate American ginseng-induced killing of colorectal cancer cells. Cancer Letters, 289 (1), 62-70. (2010).

5、Li B., Zhang R., Sun YH., and Tian WX. Inactivation Mechanism of the β-Ketoacyl-[acyl carrier protein] Reductase of Bacterial Type II Fatty Acid Synthase by pigallocatechin Gallate. Biochem. Cell Biol., 84, 755-762 (2006).

6、Li B., Ma XF., and Tian WX. Inhibitory Activity of Chlorogenic Acid on Enzymes Involved in the Fatty Acid Synthesis in Animals and Bacteria. IUBMB Life, 58, 39-46 (2006).

7、Li B., Ma XF., Wang Y., Wang X., and Tian WX. Structure-Activity Relationships for Polyphenols Inhibiting Animal Fatty Acid Synthase. J. Biochem., 138, 679-686 (2005).

8、Li B. and Tian WX. Inhibitory Effects of Flavonoids on Animal Fatty Acid Synthase. J. Biochem., 135, 85–91 (2004).

9、Li B. and Tian WX. Presence of Fatty Acid Synthase Inhibitors in the Rhizome of Alpinia officinarum Hance. J. Enzyme Inhib. Med. Chem., 18, 349–356(2003).

（肿瘤细胞生物学实验室）

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