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!
New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)
Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Physics and Astronomy
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering