After years studying the molecular bases of glioblastoma - the most common brain tumor and one of the most aggressive of all cancers, the group led by Dr. Joan Seoane , Director of Translational Research at the Vall d'Hebron Institute of Oncology (VHIO) and ICREA Research Professor has today published a study in Nature Medicine identifying USP15 as a critical protein in cancer which, thanks to its molecular characteristics, shows enormous therapeutic promise.
USP15 promotes tumor progression by activating the TGF¥â pathway. Playing a highly significant oncogenic role in glioblastoma, TGF© is a powerful immunosuppressant allowing the tumor to escape the host immune system. It also acts as an angiogenic factor inducing blood vessels, promotes tumoral invasion, activates cancer stem cells, and in some tumors, induces metastases.
USP15 as a "Biological Thermostat" at the core of a TGF¥â chain reaction
Dr. Seoane's team has unmasked the USP15 enzyme as activator of the TGF¥â chain reaction. In tumors the USP15-TGF© axis is deregulated due to USP15 gene amplification leading to an aberrant TGF© activation.
USP15 acts by controlling and correcting the TGF¥â activity in the same way that a thermostat regulates temperature. If the TGF¥â activity is high, it reduces; and if it is low, it increases the TGF¥â activity. USP15 therefore achieves optimal TGF¥â activity.
Protein stability is regulated through the elimination or aggregation of ubiquitins, small proteins that establish which molecules need to be eliminated. This process is finely regulated by deubiquitinating enzymes (DUBs) such as USP15 which determine the correct level of a protein under certain physiological conditions. In this orchestrated manner, USP15 controls and adapts the TGF¥â receptor stability and, therefore, the activity of the pathway.
The problem arises when, in some tumors, the USP15 gene is amplified due to genetic mutations and the enzyme is over produced. The thermostat breaks down and is therefore only sensing the "cold" resulting in the overactivation of the TGF¥â pathway. Remarkably, this is not only a phenomenum of glioblastomas since the USP15 gene has also been found activated in other types of cancer such as breast or ovarian cancer.
Dr. Joan Seoane explained "When we inhibited USP15 in a real model of human glioblastoma, TGF¥â activity decreased and the tumor did not develop. USP15 regulates tumor progression and is critical in cancer."
DUBs (deubiquitinating enzymes): a novel avenue in therapeutic targets
Sometimes potentially powerful therapeutic targets are found but are not pharmacologically accessible due to their biochemical characteristics. "Enzymes in general - particularly deubiquitinating enzymes (DUBs) such as USP15, can easily be deactivated and are therefore good therapeutic targets", Seoane commented, "our results, generated thanks to the funding received from the Spanish Association Against Cancer (AECC), show exciting new promise in improved treatment of cancer patients.".For further information:
Amanda Wren | EurekAlert!
Amputees can learn to control a robotic arm with their minds
28.11.2017 | University of Chicago Medical Center
The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
Transistors based on carbon nanostructures: what sounds like a futuristic dream could be reality in just a few years' time. An international research team working with Empa has now succeeded in producing nanotransistors from graphene ribbons that are only a few atoms wide, as reported in the current issue of the trade journal "Nature Communications."
Graphene ribbons that are only a few atoms wide, so-called graphene nanoribbons, have special electrical properties that make them promising candidates for the...
08.12.2017 | Event News
07.12.2017 | Event News
05.12.2017 | Event News
08.12.2017 | Life Sciences
08.12.2017 | Information Technology
08.12.2017 | Information Technology