Enzyme That Stops Progression of Kidney Cancer: Found

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By Indrani Bhattacharyya | July 22, 2014 12:45 PM EST

Kidney cancer, especially the most frequent form of it which is known as clear cell Renal Cell Carcinoma (ccRCC) has been on the rise since last decade, according to reports.

Reuters
Members of a surgical team implant a donated harvested kidney to transplant into patient Adam Abernathy as part of a five-way organ transplant swap in New York, August 1, 2012.

This form of cancer is characterised by elevated levels of glycogen and fat in the kidney cells.

The latest study, published online this week in Nature, was led by Celeste Simon, PhD, a professor of Cell and Developmental Biology and the scientific director for the Abramson Family Cancer Research Institute at Penn.

Data suggests that if these tumours are removed right after detection, a patient's prognosis for five-year survival is relatively higher.

If expression of the gene known as FBP1 is lost, patients show deterioration.

"This study is the first stop in this line of research for coming up with a personalized approach for people with clear cell renal cell carcinoma-related mutations," says Simon.

In case of ccRCC, a series of faulty reactions takes place in a biochemical pathway called Krebs cycle. As a result, this defective hyperactive Krebs cycle leads to increased level of lipid generation.

Renal cancer cells have significant association with changes in two intracellular proteins: elevated expression of hypoxia inducible factors (HIFs) and mutations in the von Hippel-Lindau (VHL) encoded protein, pVHL.

In order to find out more information, scientists looked at metabolic enzymes in the 600-plus tumors and analysed them.

The expression of FBP1 was absent in all kidney cancer tissue samples they studied.

It was observed that apart from cytoplasm where FBP1 protein are usually found, it was also present in the nucleus of these normal cells, where on binding to HIF , it regulates HIF’s effects on tumor growth.

The study reports that “in cells without FBPI, the team observed the Warburg effect -- a phenomenon in which malignant, rapidly growing tumour cells go into overdrive, producing energy up to 200 times faster than their non-cancer-cell counterparts. And since FBP1 activity is also lost in liver cancer, which is quite prevalent, FBP1 depletion may be generally applicable to a number of human cancers," Simon explained.

In the future, researchers would like to identify other metabolic pathways to determine the potential role of FBP1 in different types of human cancers.

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(Photo: Reuters / Keith Bedford)
Members of a surgical team implant a donated harvested kidney to transplant into patient Adam Abernathy as part of a five-way organ transplant swap in New York, August 1, 2012.
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