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Nature: FBP1 Enzyme——a Stumbling Block to Kidney Cancer
2014-07-24
来源：转载自第三方
24 July 2014, researchers from the Perelman School of Medicine at the University of Pennsylvania have identified an enzyme called FBP1 that can effectively block the development of kidney cancer, an enzyme that regulates the body Metabolism is crucial for binding to transcription factors in the nucleus of specific kidney cells and suppresses cellular energy metabolism, a study has been published in the international journal Nature.
The enzyme called FBP1 may be absent in all kidney tumor tissues, and the tumor cells lacking FBP1 will generate energy at high speed. When FBP1 gives play to functions normally, the uncontrolled tumor cells will be inhibited. Renal clear cell carcinoma (ccRCC) is a common kidney cancer, mainly for the glycogen level and fat accumulation of renal cell carcinoma, excessive storage will lead to accumulation of lipid droplets.
Abnormal fat accumulation in ccRCC is due to a series of erroneous biochemical reactions by the body's cells called Kreb's cycles that generate energy through carbohydrates, fats, and proteins; however, the Krebs cycle which is highly activated in the body of ccRCC patients. Therefore, it is easy to induce the increase of lipid production. Renal carcinoma cells are directly related to the changes of two important proteins in the kidney. One is high expression of hypoxia inducible factor (HIF), another is Feng-Hipel-Lindau (pVHL), in fact pVHL mutations are present in 90% of ccRCCs, and pVHL regulates HIFs, thereby affecting the activity of the Krebs cycle.
In order to reveal the epigenetic properties of the enzyme FBP1, the team conducted a study of metabolic enzymes in more than 600 tumor tissues. FBP1 was found to be absent in all renal cell carcinoma tissues. FBP1 expression was observed in the cytoplasm of normal cells. In the absence of FBP1, the researchers observed a Warburg effect, which means that under aerobic conditions, the tumor cells were still primarily supplied with glycolysis, which would lead to overgrowth of tumor cells, and the rate of energy to produce is 200 times than non-cancer cells.
The unique dual function of FBP1 may help explain why it is absent in the ccRCC. The absence of FBP1 may be used to study the genesis of human cancers. The next step will be to identify other metabolic pathways in the body and to determine the role of FBP1 enzymes in the process of disease development, and to provide a scientific basis for mouse models and preclinical study. (Suzhou Yacoo)
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