Researchers headed by Erwin Wagner, the Director of the BBVA Foundation-CNIO Cancer Cell Biology Programme at the Spanish National Cancer Research Centre (CNIO), have deciphered how a stress-inducible gene regulator, AP-1, controls the survival of liver tumor-initiating cells. These results, published in the online edition of Nature Cell Biology, could provide new preventive strategies and identify potentially targetable molecules to prevent liver cancer.
Hepatocellular carcinoma (HCC) causes more than 500,000 deaths per year worldwide. While patients with chronic hepatitis virus B and C infections or liver cirrhosis are high-risk populations for HCC, measures aiming at preventing HCC development in these patients are limited. In addition, the long-term prognosis after surgical resection of HCC remains poor, due to the high rate of de novo recurrence and the lack of effective preventive therapy.
The critical step for developing effective preventive therapies, but also diagnostic markers and preventive strategies is to identify targetable molecules and pathways responsible for cancer initiation.
Using genetic mouse models specific for liver cancer initiation, researchers have discovered how the stress-inducible AP-1 gene regulator modulates liver tumor cell death in early stages of liver cancer. Mechanistically, AP-1 controls the expression of the epigenetic modulator SIRT6. Subsequently, SIRT6 represses Survivin, which is involved in programmed cell death.
Importantly, altering these proteins in mice even transiently during the initiation stage markedly impaired liver cancer development in mice.
The relevance of these findings was tested in more than 150 human tissue samples collected in patients from Asia and Europe. A clear correlation between these proteins and liver cancer initiation, but not in advanced HCCs, was observed.
These results connect liver cancer initiation with epigenetics and cell death, and give new insights into why patients with metabolic diseases where SIRT6 is important, are at risk of developing of liver cancer.
"Our study provides not only novel implications for the development of preventive therapies for high risk cirrhotic or post-resection patients, but also a new paradigm how one can molecularly dissect cancer initiation using mouse models in combination with the appropriate human samples", states Latifa Bakiri, author of the study.
The study was initiated in Erwin Wagner´s group at the IMP in Vienna and subsequently carried out at the Spanish National Cancer Research Centre (CNIO) and at the State Key Laboratory of Cell Biology, in Shanghai China led by Lijian Hui.
The study also involves the participation of clinical researchers at Fudan University in Shanghai and the Medical University of Graz, Austria.
Juan J. Gomez | EurekAlert!
Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg
The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision
Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...
19.07.2017 | Event News
12.07.2017 | Event News
12.07.2017 | Event News
20.07.2017 | Information Technology
20.07.2017 | Materials Sciences
20.07.2017 | Physics and Astronomy