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!
Scientists discover species of dolphin that existed along South Carolina coast
24.08.2017 | New York Institute of Technology
The science of fluoride flipping
24.08.2017 | University of North Carolina Health Care
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
24.08.2017 | Life Sciences
24.08.2017 | Life Sciences
24.08.2017 | Medical Engineering