In a study published online this week in the Proceedings of the National Academy of Sciences, scientists at the Ludwig Institute for Cancer Research in Oxford discovered a critical molecular switch that regulates autophagy. They also studied the links between autophagy and a cellular process called senescence that stops cell growth permanently.
The researchers identified ASPP2, a tumor suppressor, as a molecular switch that can dictate the ability of a common cancer gene, known as the RAS oncogene, to either stop or promote senescence.
As Yihua Wang and researchers in Xin Lu's group at the Ludwig Institute investigated the life cycle of fibroblast cells – the most common connective tissue cells in animals – they found that reduced levels of the ASPP2 protein increase RAS oncogene-induced autophagic activity. This in turn prevented cells from entering senescence. Without ASPP2, the cells continued to proliferate unchecked, thereby promoting tumor growth.
ASPP2 is known to play a role in suppressing tumor development. Mice that have a deficiency or malfunction in this protein have a predisposition to developing tumors. And low ASPP2 levels in patients are linked to poor prognoses in cancers, such as large B-cell lymphomas. Reduced ASPP2 expression has also been observed in highly metastatic breast tumors. But until now, researchers did not understand why.
"We found that in the presence of the common cancer-causing RAS oncogene, ASPP2 interacted with a protein complex that is responsible for deciding cell fate via autophagy," said Yihua Wang, PhD, Ludwig researcher in Oxford.
"What this means is that the cell's emergency stop button is disabled when ASPP2 expression is reduced or lost, allowing it to proliferate unchecked as with cancer," added Wang.
"The balance between the RAS oncogene and ASPP2 activity is crucial to determining whether or not tumor growth is promoted. Our next step will be to identify ways to alter ASPP2 activity at that critical switch point. This could be an effective way to treat cancers with reduced ASPP2 expression and mutated RAS, such as breast and colon cancers," concluded Wang.
"Some of the recently developed anti-cancer drugs are potent inducers of autophagy. The new findings may also offer an explanation as to why patient response to these drugs can vary dramatically. There are factors at play within the body that can dictate authophagic activity and impact clinical outcomes," said Xin Lu, PhD, director of Ludwig's Oxford Branch. "While further study is needed, these findings may in the longer term help doctors to identify patients who are more likely to respond well to autophagic inhibition," added Lu.
About The Ludwig Institute for Cancer Research
LICR is an international non-profit organization committed to improving the understanding and control of cancer through integrated laboratory and clinical discovery. Leveraging its worldwide network of investigators and the ability to sponsor and conduct its own clinical trials, the Institute is actively engaged in translating its discoveries into applications for patient benefit. Since its establishment in 1971, the Institute has expended more than $1.5 billion on cancer research.
Rachel Steinhardt | EurekAlert!
The Secret of the Rock Drawings
24.05.2019 | Max-Planck-Institut für Chemie
Chemical juggling with three particles
24.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn
A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.
The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...
Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.
The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...
Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...
With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.
Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...
'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.
However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
24.05.2019 | Physics and Astronomy
24.05.2019 | Medical Engineering
24.05.2019 | Life Sciences