Understanding the Linkage between Glucose-Lipid Metabolism and Tumorigenesis in the Human Prostate Carcinoma Cells

The metabolic pathways of cancer cells are reprogrammed including aerobic glycolysis, fatty acid and nucleotide synthesis to satisfy tumor cells proliferation and survival requirement. To evaluate and characterize the regulatory mechanisms of the glucose-lipid metabolism on the tumor markers will allow us to understand and develop a new diagnosis and treatment of prostate. Previous studies from PI’s laboratory have succeeded in not only understanding the regulatory mechanism of mitochondrial aconitase (mACON) and fatty acid synthase (FASN) in the glucose-lipid metabolism but also evaluating the metabolism modulators including Live X receptor (LXRs), ChoRE-binding protein (ChREBP), hypoxia induce factor 1 (HIF1), androgen receptor (AR), p53, and phosphatase and tensin homologue (PTEN) on the tumorigenesis of prostate carcinoma cells. PI’s preliminary data revealed that sterol response element binding protein (SREBPs) and PTEN dyregulated the expressions of FASN, cell proliferation modulator, B-Cell translocation gene 2 (BTG2), and tumor marker, prostate specific antigen (PSA) in prostate carcinoma cells. Although glucose-lipid metabolism have been studied extendedly, the contrary or not consistence results were eluded when using various commercial prostate cell lines due to the quite different characteristics including the status of AR, PTEN, p53, LXRs, SREBPs.. etc of those cells. PI will integrate the knowledge from previous studies of PI’s laboratory including prostate tumor biology, cellular metabolism, and molecular endocrinology, and use the gene regulation approach to (1) identify the SREBPs as the sensor of glucose and lipid metabolism in the prostate carcinoma cells, (2) identify the SREBP as a modulator of tumorigenesis in the prostate carcinoma cells, and (3) understand the regulatory mechanisms among the SREBPs, LXRs, AR, PTEN, p53, and HIF1 in prostate carcinoma cells in this three-year proposal. The novel data from this proposal will provide the understanding of the regulatory mechanisms between glucose-lipid metabolism and tumorigenesis in the neoplastic of the prostate, and except to employ these concepts in the early diagnosis and drug screen of the disease of prostate.

Project ID:PC10507-0246
External Project ID:MOST105-2320-B182-020-MY3