![[ Back to EurekAlert! ]](http://www.eurekalert.org/images/back2e.gif){kind=small}
Public release date: 15-Apr-2013[ | E-mail |
Share ] Contact: Juha Klefstr?m
juha.klefstrom@helsinki.fi
358-919-125-493
University of Helsinki
ATP is the main energy currency of cells and one might expect that not only contracting muscle, but also uncontrollably dividing cancer cells would have a high demand for ATP. However, for some reason cancer cells have re-programmed their metabolic engines to produce less ATP. The phenomenon, known as Warburg effect, is typical for cancer cells and the mechanism behind is believed to benefit cancer cells by switching biochemical engines from energy manufacturing reactions to anabolic reactions, which primarily support growth of the cell size and proliferation.
The triggers for "non-stop" proliferation programs in cancer cells are the tumor-promoting oncoproteins, like protein called Myc. Luckily, it seems that oncoproteins are not perfect programmers.
Finnish scientists from the University of Helsinki, investigating how Myc re-engineers metabolic pathways in cells, have identified an unexpected branch in the pathway - a branch that ends to cell death (apoptosis).
The researchers found that Myc activates cancer-like changes in cell metabolism, causing a sudden fall in ATP concentration inside the cells. Declining ATP levels awake a bioenergy sensor protein known as AMP kinase (AMPK), which starts a biochemical chain of events moving a tumor suppressor protein p53 to the surface of the mitochondria. At mitochondria, p53 activates apoptosis-promoting proteins, the investigation suggests.
According to University of Helsinki scientist and Finnish Academy Research Fellow Juha Klefstrm, PhD, who led the study, "Myc oncoprotein not only boosts tumor cell proliferation but it also makes the cells vulnerable to cell suicide program, apoptosis. The cancer gene dependent vulnerability to apoptosis has promise to be the prime target for future targeted cancer therapies but first, we need to understand the cell pathways that are causing this vulnerability. The investigated connections between Myc, energy metabolism and apoptosis will help us to understand the biochemistry of cancer cell apoptosis. However, the finding is also interesting from a therapeutic standpoint since there are many drug-like molecules that can be used to turn on and off the AMPK controlled pathways in cancer cells."
Healthy cells may encounter ATP and energy shortage for example, during strenuous exercise, so that alone is not sufficient to kill the cells. Why then Myc oncoprotein transformed cells succumb to ATP deprivation?
A graduate student Anni Nieminen, the first author in the study explains, "In healthy cells dwindling ATP levels signals activation of AMPK, which tells the cells to save energy, for example, by stopping the cell proliferation. The resting cells can then restock ATP supplies before entering the energy consuming proliferation again. However, cells with active Myc cannot stop the cell cycle engine and we think that the non-stop proliferation of the cells with low ATP content leads to prolonged activation of AMPK and p53. Gradual increase of p53 levels activates apoptosis promoting protein Bak on the surface of the mitochondria making these cells vulnerable to death. The inability of Myc transformed cells to rest and recover could explain why Myc makes cells so vulnerable to apoptosis."
How can these cancer cell specific metabolic pathways and reactions be targeted with drugs?
According to Juha Klefstrm, "For example, recent epidemiological studies have shown that a diabetes drug metformin, which acts as an AMPK activator, may reduce the risk of cancer. It is often claimed that a drug-induced AMPK activation starves cancer cells to death. Our study suggests that AMPK can speak directly to the cells' death machinery, which opens new possibilities to exploit the AMPK pathway for cancer therapy."
The study will be published in the Proceedings of the National Academy of Sciences (PNAS) Online Early Edition on the 15th April, 2013.
###
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Public release date: 15-Apr-2013[ | E-mail |
Share ] Contact: Juha Klefstr?m
juha.klefstrom@helsinki.fi
358-919-125-493
University of Helsinki
ATP is the main energy currency of cells and one might expect that not only contracting muscle, but also uncontrollably dividing cancer cells would have a high demand for ATP. However, for some reason cancer cells have re-programmed their metabolic engines to produce less ATP. The phenomenon, known as Warburg effect, is typical for cancer cells and the mechanism behind is believed to benefit cancer cells by switching biochemical engines from energy manufacturing reactions to anabolic reactions, which primarily support growth of the cell size and proliferation.
The triggers for "non-stop" proliferation programs in cancer cells are the tumor-promoting oncoproteins, like protein called Myc. Luckily, it seems that oncoproteins are not perfect programmers.
Finnish scientists from the University of Helsinki, investigating how Myc re-engineers metabolic pathways in cells, have identified an unexpected branch in the pathway - a branch that ends to cell death (apoptosis).
The researchers found that Myc activates cancer-like changes in cell metabolism, causing a sudden fall in ATP concentration inside the cells. Declining ATP levels awake a bioenergy sensor protein known as AMP kinase (AMPK), which starts a biochemical chain of events moving a tumor suppressor protein p53 to the surface of the mitochondria. At mitochondria, p53 activates apoptosis-promoting proteins, the investigation suggests.
According to University of Helsinki scientist and Finnish Academy Research Fellow Juha Klefstrm, PhD, who led the study, "Myc oncoprotein not only boosts tumor cell proliferation but it also makes the cells vulnerable to cell suicide program, apoptosis. The cancer gene dependent vulnerability to apoptosis has promise to be the prime target for future targeted cancer therapies but first, we need to understand the cell pathways that are causing this vulnerability. The investigated connections between Myc, energy metabolism and apoptosis will help us to understand the biochemistry of cancer cell apoptosis. However, the finding is also interesting from a therapeutic standpoint since there are many drug-like molecules that can be used to turn on and off the AMPK controlled pathways in cancer cells."
Healthy cells may encounter ATP and energy shortage for example, during strenuous exercise, so that alone is not sufficient to kill the cells. Why then Myc oncoprotein transformed cells succumb to ATP deprivation?
A graduate student Anni Nieminen, the first author in the study explains, "In healthy cells dwindling ATP levels signals activation of AMPK, which tells the cells to save energy, for example, by stopping the cell proliferation. The resting cells can then restock ATP supplies before entering the energy consuming proliferation again. However, cells with active Myc cannot stop the cell cycle engine and we think that the non-stop proliferation of the cells with low ATP content leads to prolonged activation of AMPK and p53. Gradual increase of p53 levels activates apoptosis promoting protein Bak on the surface of the mitochondria making these cells vulnerable to death. The inability of Myc transformed cells to rest and recover could explain why Myc makes cells so vulnerable to apoptosis."
How can these cancer cell specific metabolic pathways and reactions be targeted with drugs?
According to Juha Klefstrm, "For example, recent epidemiological studies have shown that a diabetes drug metformin, which acts as an AMPK activator, may reduce the risk of cancer. It is often claimed that a drug-induced AMPK activation starves cancer cells to death. Our study suggests that AMPK can speak directly to the cells' death machinery, which opens new possibilities to exploit the AMPK pathway for cancer therapy."
The study will be published in the Proceedings of the National Academy of Sciences (PNAS) Online Early Edition on the 15th April, 2013.
###
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-04/uoh-ccm041213.php
ohio state basketball collateral dick cheney heart umf elite eight stephon marbury the lion king
In the first interview since her husband’s death, Laurene Powell Jobs dedicated her sizable platform to advancing immigration reform, while remaining notably tight-lipped about the private life of the late Steve Jobs. We’ve included highlights (with context) from her interview with Rock Center host Brian Williams. On Steve Jobs: “Pretty Cool” Legacy BRIAN WILLIAMS: It’s another way of saying we’re left with a world of really cool stuff. I always wanted to know what it was like to be a Kennedy and drive to Kennedy Airport; and what it’s like to be you at a light and watch 10 people cross, and the only thing they have in common are white ear buds. What’s that like? LAURENE POWELL JOBS: It’s pretty cool. BRIAN WILLIAMS: (LAUGHS) It’s pretty cool. I mean, that changed our world. LAURENE POWELL JOBS: Yeah. To do what you wanna do, to leave a mark– in a way that you think is important and lasting, that’s a life well lived. On Immigration Reform Powell Jobs has been a vocal advocate of immigration reform, partnering with director Davis Guggenheim (Waiting For Superman, An Inconvenient Truth) on a documentary highlighting the struggles of talented, patriotic American youth who have been denied entrance into the military and college because they are undocumented immigrants. To add public pressure for Congress to pass a bill that provides a pathway to citizenship for children of immigrants who came to America illegally, the film (trailer below) is accompanied by a grassroots campaign and website. BRIAN WILLIAMS: Climb into the minds of our viewers watching you guys on Friday night. So help us process this. How are we supposed to feel about their parents, who did do something bad? This is ill-gotten gains, because the first entry into this country was wrong. How are we supposed to feel about the bureaucracy we would now have to have just to hand Social Security numbers to our Marine, our civil engineer? LAURENE JOBS POWELL: Yes. It’s understandable that people are conflicted about this. And, yes, the parents broke the law. And so I think that’s why Congress is trying to find a way to make amends. So have them pay a penalty, have them pay back taxes. Have them wait for two decades in order to have the chance to have citizenship. I mean, there are penalties that can be brought out. But then you have someone
?