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The stress and cancer link: 'Master switch' stress gene enables cancer's spread
Date:8/22/2013

r's development, this process typically works.

But as cancer cells grow and thrive in a tumor, they send out certain molecular messengers to promote a chronic wound-healing response. Cancer cells, by acting like a wound that never heals, hijack this process to help themselves survive and spread.

"ATF3 induction in immune cells is one way this probably happens. We're not saying it's the only way," Hai said.

ATF3 is a master switch type of gene: Its gene product, the ATF3 protein, turns on and off other genes. Knowing this, the researchers analyzed the genes that are controlled by ATF3 using a genome-wide global approach. Combining this set of data with another set of data from human samples, Hai and colleagues were able to identify an ATF3 gene signature that can predict whether cancer patients had a low or high risk of dying.

"Since our global gene analysis was carried out using samples from mouse models, our ability to identify a gene signature to partition patients into high risk or low risk suggests that our mouse model has relevance to human breast cancer," she said.

Though the work suggests a drug to dampen ATF3's effect could lower the risk for metastasis, Hai noted that scientists don't fully understand what the overall effects of that dampening would be.

"We have this gene for a reason. It's a gene that helps us adapt to changes. So it's a question of how and when to target ATF3," she said.

There are lots of ways to turn on ATF3 in cells, and stress signals sent out by cancer cells represent just one method to express this gene in immune-system cells and produce a chronic would-healing response. Other ways include radiation, chemotherapeutic agents, a high-fat diet, UV damage and even chronic behavioral stress.

Hai plans to test whether these other kinds of stressors also affect the immune cells through ATF3 induction, changing them from attacking cancer cells to helping cancer cell
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Contact: Tsonwin Hai
Hai.2@osu.edu
614-292-2910
Ohio State University
Source:Eurekalert

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