| Table of Contents | 第3-5页 |
| Abstract | 第5-7页 |
| 中文摘要 | 第8-11页 |
| Abbreviations/Acronyms | 第11-12页 |
| ChapterⅠ Disordered metabolism in urothelial carcinoma of bladder | 第12-58页 |
| 1. The overview of urothelial carcinoma of bladder(UCB) | 第13-25页 |
| 1.1 The types of UCB | 第14-15页 |
| 1.1.1 Transitonal cell carcinoma(TCC) | 第14-15页 |
| 1.1.2 Squamous cell carcinoma | 第15页 |
| 1.1.3 Adenocarcinoma | 第15页 |
| 1.1.4 Small cell carcinoma | 第15页 |
| 1.2 Genetic and molecular events in UCB | 第15-17页 |
| 1.2.1 Early stage cytogenetic changes in UCB | 第16-17页 |
| 1.2.2 Advanced stage cytogenetic changes | 第17页 |
| 1.3 Disregulated molecules in UCB | 第17-25页 |
| 1.3.1 Activation of RTK-Ras | 第18-20页 |
| 1.3.2 Defects of p53 and RB pathways | 第20-21页 |
| 1.3.3 Activation of STAT3 pathways | 第21-23页 |
| 1.3.4 Dysregulation of AR signal pathway | 第23-25页 |
| 2. Disordered metabolism in UCB | 第25-39页 |
| 2.1 Glucose and lipid metabolism in UCB | 第27-29页 |
| 2.2 Molecular basis of glucose and fatty acid metabliosm in UCB | 第29-35页 |
| 2.2.1 Disregulated proteins in glucose and fatty acid metabolism | 第30-32页 |
| 2.2.2 Overactived FGFR3/Ras in glucose and fatty acid metabolism | 第32-33页 |
| 2.2.3 Disfunctin of p53 in glucose and fatty acid metabolism | 第33-34页 |
| 2.2.4 Amplification of MYC in glucose and fatty acid metabolism | 第34-35页 |
| 2.2.5 Enhanced stability of HIF1α in glucose and fatty acid metabolism | 第35页 |
| 2.3 Glucose metabolism and lipogenesis accelerate cancer proliferation | 第35-37页 |
| 2.4 Glucose and lipid metabolism roles in cancer mircoenvironment | 第37-38页 |
| 2.5 Glucose and lipid metabolism roles in histone modification | 第38-39页 |
| 3. Target glucose and fatty acid metabolism | 第39-42页 |
| 4. Conclusions and Therapentic Perspectives | 第42-44页 |
| 5. Reference | 第44-58页 |
| Chapter Ⅱ SRC-3 regulates glucose metabolism in bladder cancer cells through coactivation of HIF1α | 第58-87页 |
| 1. Abstract | 第59-60页 |
| 2. Introduction | 第60-62页 |
| 3. Materials and methods | 第62-67页 |
| 3.1 Tissue samples,cell lines,plasmids and reagents | 第62页 |
| 3.2 Generation of stable SRC-3 knockdown and overexpression cells,cell proliferation and soft agar assays | 第62-63页 |
| 3.3 Quantitative RT-PCR | 第63-64页 |
| 3.4 Immunoprecipitation,GST pull-down and Western blotting assays | 第64页 |
| 3.5 Luciferase assay | 第64-65页 |
| 3.6 Chromatin immunoprecipitation assay | 第65页 |
| 3.7 Glucose,lactate,media pH and ATP production measurements | 第65页 |
| 3.8 Immunohistochemistry | 第65-66页 |
| 3.9 Tumor xenograft | 第66页 |
| 3.10 Statistics analysis | 第66-67页 |
| 4. Results | 第67-80页 |
| 4.1 Overexpression of SRC-3 in UBC cells enhances aerobic glycolysis | 第67-70页 |
| 4.2 SRC-3 deficiency impairs glycolysis in bladder cancer cells under hypoxic conditions | 第70-71页 |
| 4.3 Suppression of SRC-3 inhibits tumorigenicity | 第71-73页 |
| 4.4 SRC-3 coactivates HIF1α transcriptional activity | 第73-76页 |
| 4.5 Inhibition of glycolysis pathway suppresses SRC-3 induced cell proliferation | 第76-77页 |
| 4.6 Positive correlation between SRC-3 and HIF1α-regulated genes in the glycolytic pathway in human UBC specimens | 第77-80页 |
| 5. Discussion | 第80-83页 |
| 6. References | 第83-87页 |
| Chapter Ⅲ SRC-3 promotes bladder cancer stemness through increasing de novo lipogenesis | 第87-113页 |
| 1. Abstract | 第88-89页 |
| 2. Introduction | 第89-91页 |
| 3. Material and Method | 第91-96页 |
| 3.1 Tissue samples,cell lines,plasmids and reagents | 第91页 |
| 3.2 Generation of stable SRC-3 knockdown and overexpression cells,sphere formation assays | 第91-92页 |
| 3.3 Quantitative RT-PCR | 第92页 |
| 3.4 Immunoprecipitation and GST pull-down | 第92页 |
| 3.5 Luciferase assay | 第92-93页 |
| 3.6 Chromatin immunopreciptation assay | 第93页 |
| 3.7 Lipid accumulation measurements | 第93页 |
| 3.8 lmmunohistochemistry | 第93-94页 |
| 3.9 Flow cytometry analysis | 第94页 |
| 3.10 Statistics analysis | 第94-96页 |
| 4. Results | 第96-108页 |
| 4.1 Overexpression of SRC-3 is correlated with lipid accumulation in bladder cancer | 第96-99页 |
| 4.2 SRC-3 can enhance bladder cancer stemness maintenance through upregulatioin of de novo lipogenesis | 第99-103页 |
| 4.3 SRC-3 coactives SREBP-1c to regulate de novo lipogenic genes expression | 第103-105页 |
| 4.4 SRC-3 mediates IKKs signal to lipogenic genes regulation | 第105-108页 |
| 5. Discussion | 第108-110页 |
| 6. Reference | 第110-113页 |
| Summary and Further Plan | 第113-115页 |
| 致谢 | 第115-116页 |
| Publications | 第116-118页 |
