The researchers, led by Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT, found the alteration while studying a mouse model of lung cancer. They then compared their mouse data to genetic profiles of human lung tumors and found that reduced activity of the same gene, NKX2-1, is associated with higher death rates for lung-cancer patients.
This study represents an important step in understanding how changes that disable this gene would make tumors more aggressive, says Monte Winslow, a senior postdoctoral associate in Jacks’ lab and lead author of a paper.
Understanding the role of NKX2-1 may help scientists pursue drugs that could counteract its loss. Right now, “the sad reality is that if you could tell a patient whether their cancer has turned down this gene, you would know they will have a worse outcome, but it wouldn’t change the treatment,” Winslow says.
Winslow and his colleagues at the Koch Institute studied mice that are genetically programmed to develop lung tumors. The mice’s lung cells can be induced to express an activated form of the cancer-causing gene Kras, and the tumor suppressor gene p53 is deleted. While all of those mice develop lung tumors, only a subset of those tumors metastasizes, suggesting that additional changes are required for the cancer to spread.
The researchers analyzed the genomes of metastatic and non-metastatic tumors in hopes of finding some genetic differences that would account for the discrepancy. The absence of NKX2-1 activity in metastatic tumors was the most striking difference, Winslow says.
The NKX2-1 gene codes for a transcription factor — a protein that controls expression of other genes. Its normal function is to control development of the lung, as well as the thyroid and some parts of the brain. When cancerous cells turn down the expression of the gene, they appear to revert to an immature state and gain the ability to detach from the lungs and spread through the body, seeding new tumors.
Once the researchers identified NKX2-1 as a gene important to metastasis, they started to look into the effects of the genes that it regulates. They zeroed in on a gene called HMGA2, which had been previously implicated in other types of cancer. It appears that NKX2-1 represses HMGA2 in adult tissues. When NKX2-1 is shut off in cancer cells, HMGA2 turns back on and helps the tumor to become more aggressive.
They also found that human tumors with NKX2-1 missing and HMGA turned on tended to be metastatic, though not all metastatic tumors fit that profile.
It would be difficult to target NKX2-1 with a drug because it’s much harder to develop drugs that turn a gene back on than shut it off, Winslow noted. A more promising possibility is targeting HMGA2 or other genes that NKX2-1 represses.
Jacks’ lab is now looking at other types of cancer, to see if NKX2-1 or HMGA2 have the same role in other metastatic cancers. “It’s great to find something that’s important in lung cancer metastasis, but it would be even better if it controlled metastasis in even a subset of other cancer types,” Winslow says.
Patti Richards | Newswise Science News
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
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
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences