Science News - March 26, 2011

cancer cells escape from the main tumor.

To get some clues about how tough a hungry cancer call can be, White and her colleagues made cells unable to commit suicide, a hallmark of cancer cells. Then the team starved the cells.

Even cells that can’t kill themselves would die eventually if they didn’t get enough nutrients, the researchers thought. But in the lab, these cancerlike cells seemed to do just fine without food. “When we looked at them closely, we realized they were eating themselves,” White says.

As these starving cells munched away on themselves, becoming smaller and smaller, they eventually went dormant, existing but not doing much else. That dormant state can last a week or a month, depending on the type of cell, White says. But when the cells were no longer under so much stress, they rebounded and began growing again.

Cancer cells in the body may use a similar strategy to hide and ride out tough times, then cause a relapse later. “These are what we call the oncology horror movies,” White says.

Although scenes of hungry zombie tumors rising from the dead are terrible, scientists aren’t throwing their hands over their faces and cowering. Instead, researchers are experimenting with therapies that may ruin cancer cells’ self-eating picnics. Clinical trials are currently under way to determine if drugs that block autophagy, such as hydroxychloroquine, can make cancer cells more vulnerable to chemotherapy.

Dialed up Researchers have found that a drug for high blood pressure boosts autophagy in mice with Huntington’s disease, decreasing levels of the toxic huntingtin protein. Scientists aren’t sure if the drug works in people.

SouRce: clAudiA RoSe e T al/ HumaN molecular geNe Tics 2010

Drug’s effect on autophagy levels

Levels of a protein found on autophagosomes (%)*

400

300

200

100

0

Rilmenidine Control *Relative to tubulin, a cell protein

Drug’s effect on huntingtin levels

120

Levels of huntingtin protein (%)**

40 100

80

60

20

0

Rilmenidine Control **Relative to actin, a cell protein

Balance for the brain

Controlling autophagy may also be the key to quashing neurodegenerative diseases. Though researchers have known that autophagy is messed up in several neuron-killing diseases, only recently have the details come to light.

“In many of these diseases we’re getting some quite good clues about what is going wrong when,” says David Rubinsztein of the Cambridge Institute for Medical Research and Cambridge University in England.

For instance, in Parkinson’s disease
globs of a protein called alpha-synuclein
build up in the cell and stop autophago-
somes from swallowing, Rubinsztein and
his colleagues reported last year in the
Journal of Cell Biology. With the cell’s
chomping abilities lost, the toxic protein
continues to build up, eventually leading
to the death of the cell. The same is true
of Huntington’s disease: Autophagy can’t
do its part because of toxic levels of the
huntingtin protein, Rubinsztein and oth-
ers have found.