Landmark study describes prostate cancer metastasis switch

Loss of E-Cadherin allows metastasis -- CU Cancer Center researchers make cancer cells restart production

2013-04-02

(Press-News.org) Prostate cancer doesn't kill in the prostate – it's only once the disease travels to bone, lung, liver, etc. that it turns fatal. Previous studies have shown that loss of the protein E-Cadherin is essential for this metastasis. A University of Colorado Cancer Center study published this week in the Journal of Biological Chemistry describes for the first time a switch that regulates the production of E-Cadherin: the transcription factor SPDEF turns on and off production, leading to metastasis or stopping it cold in models of prostate cancer.

"When E-Cadherin is lost, cells become 'rouge' – they can detach from their surrounding tissues, move effortlessly through the circulatory system, grow and attach at new sites. In prostate tumors that had lost E-Cadherin, we put in SPDEF and the tumors once again expressed E-Cadherin. They were once again anchored in place and unable to metastasize. We can make these 'rouge' cells back into epithelial-like cells and these epithelial cells stay anchored and lose the ability to migrate," says Hari Koul, PhD, investigator at the CU Cancer Center and professor and director of Urology Research at the University of Colorado School of Medicine, the study's senior author.

In fact, the work could have implications far beyond prostate cancer, as increasing evidence points to loss of E-Cadherin as a prerequisite for metastasis in many cancers. Koul and colleagues first showed that E-Cadherin levels varied directly with the addition or subtraction of SPDEF. Then the group artificially knocked down E-Cadherin despite the presence of SPDEF and showed that cells remained able to migrate and invade new tissues (SPDEF didn't by itself affect metastasis and was instead dependent on modulating E-Cadherin, which is the driver). The group also showed a one-way switch – SPDEF regulates E-Cadherin, but E-Cadherin expression does nothing to affect levels of SPDEF.

"Taken together, these studies paint a pretty compelling picture of SPDEF working in part through the modulation of E-Cadherin to inhibit prostate cancer metastasis," Koul says. "To the best of our knowledge these are the first studies demonstrating the requirement of SPDEF for expression of E-Cadherin."

Koul says that his group is getting very close to turning off the loss of E-Cadherin in cancer cells by re-arming tumors with the gene that makes SPDEF and my testing small molecules that increase SPDEF in cancer cells.

"This could be a real landmark," Koul says. "We see a prerequisite for metastasis and now we have a very clear picture of how to remove this necessary condition for the most dangerous behavior of prostate cancer."

### END

ELSE PRESS RELEASES FROM THIS DATE:

College athletes twice as likely to have depression than retired collegiate athletes

2013-04-02

WASHINGTON — A survey of current and former college athletes finds depression levels significantly higher in current athletes, a result that upended the researchers' hypothesis. The finding published in Sports Health suggests the need for more research to understand depression among college athletes. "We expected to see a significant increase in depression once athletes graduated, but by comparison it appears the stress of intercollegiate athletics may be more significant than we and others anticipated," says the study's senior investigator Daniel Merenstein, MD, an associate ...

Annals of Internal Medicine tip sheet for April 2, 2013

2013-04-02

1. For Greater Weight Loss, a Group Cash Incentive Trumps Individual Rewards A group-based financial incentive leads to greater weight loss than an individual incentive for obese employees. An estimated 67 percent of employers use financial incentives to help their employees adopt healthier behaviors, with the goal of decreasing chronic disease and curbing health care costs. Researchers sought to determine the effectiveness of two financial incentive designs – group-based and individual – for obese employees trying to lose weight. One-hundred-and-four employees with a ...

Cash for weight loss? Works better when employees compete for pots of money, study finds

2013-04-02

ANN ARBOR, Mich. — Do cash rewards for healthier habits work? Maybe, says a new study, if you add on one more condition – peer pressure. A growing number of companies are offering employees an opportunity to boost earning power at work via cash incentives to stay healthy. Under the Affordable Care Act, employers will soon be able to offer even larger financial incentives to prod healthy lifestyle behaviors among their workforce, such as quitting smoking and losing weight. But people who are offered money for weight loss may be much more successful when awards are ...

Post-ER care for chest pain reduces risk of heart attack, death

2013-04-02

Seeing a doctor within a month of an emergency room visit for chest pain significantly reduced the risk of heart attack or death among high risk patients, according to research published the American Heart Association journal Circulation. Chest pain is the most common reason people go to the emergency room in developed countries and accounts for more than 5 million ER visits each year in the United States. The study is the first to demonstrate the importance of follow-up care for chest pain patients after leaving the ER, researchers said. High risk patients in this study ...

Understanding statin discontinuation

2013-04-02

Boston, MA-- Despite their well-documented benefits, statins, drugs used to lower cholesterol, are commonly discontinued in routine care. Statin discontinuation has been linked to increased risk for cardiovascular events and death in patients with coronary artery disease; nevertheless, the reasons for discontinuation are only starting to be explored. In a new study from Brigham and Women's Hospital (BWH), researchers examined the role adverse reactions play in statin discontinuation and found that more than 90 percent of the patients who stopped taking a statin due to an ...

Extreme algal blooms: The new normal?

2013-04-02

Washington, D.C.—A research team, led by Carnegie's Anna Michalak, has determined that the 2011 record-breaking algal bloom in Lake Erie was triggered by long-term agricultural practices coupled with extreme precipitation, followed by weak lake circulation and warm temperatures. The team also predicts that, unless agricultural policies change, the lake will continue to experience extreme blooms. The research is published in the online early edition of the Proceedings of the National Academy of Sciences the week of April 1, 2013. "The perfect storm of weather events ...

Record-breaking 2011 Lake Erie algae bloom may be sign of things to come

2013-04-02

ANN ARBOR—The largest harmful algae bloom in Lake Erie's recorded history was likely caused by the confluence of changing farming practices and weather conditions that are expected to become more common in the future due to climate change. Rather than an isolated, one-time occurrence, Lake Erie's monumental 2011 algae bloom was more likely a harbinger of things to come, according to University of Michigan researchers and colleagues from eight other institutions. The interdisciplinary team explored factors that may have contributed to the event and analyzed the likelihood ...

Body Mass Index and coronary heart disease

2013-04-02

Coronary heart disease (CHD) increases with BMI, as well as with age, finds an article published in BioMed Central's open access journal BMC Medicine. The research from the Million Women Study indicates that increased weight increases risk of CHD equivalent to that caused by getting older. Researchers from the University of Oxford followed the health of 1.2 million women from England and Scotland for (on average) almost a decade. Analysis of the data showed that the occurrence of CHD increases with BMI so that every 5 unit increase in BMI, calculated as weight/height2, ...

Tests to predict heart problems may be more useful predictor of memory loss than dementia tests

2013-04-02

MINNEAPOLIS – Risk prediction tools that estimate future risk of heart disease and stroke may be more useful predictors of future decline in cognitive abilities, or memory and thinking, than a dementia risk score, according to a new study published in the April 2, 2013, print issue of Neurology®, the medical journal of the American Academy of Neurology. "This is the first study that compares these risk scores with a dementia risk score to study decline in cognitive abilities 10 years later," said Sara Kaffashian, PhD, with the French National Institute of Health and Medical ...

Eating fish associated with lower risk of dying among older adults

2013-04-02

Boston, MA – Older adults who have higher levels of blood omega-3 levels—fatty acids found almost exclusively in fatty fish and seafood—may be able to lower their overall mortality risk by as much as 27% and their mortality risk from heart disease by about 35%, according to a new study from Harvard School of Public Health (HSPH) and the University of Washington. Researchers found that older adults who had the highest blood levels of the fatty acids found in fish lived, on average, 2.2 years longer than those with lower levels. "Although eating fish has long been considered ...

In small preliminary study, fearful pet dogs exhibited significantly different microbiomes and metabolic molecules to non-fearful dogs, suggesting the gut-brain axis might be involved in fear behavior

[Press-News.org] Landmark study describes prostate cancer metastasis switch
Loss of E-Cadherin allows metastasis -- CU Cancer Center researchers make cancer cells restart production

Landmark study describes prostate cancer metastasis switch

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: