In laboratory experiments, scientists have eliminated metastasis, the spread of cancer from the original tumor to other parts of the body, in melanoma by inhibiting a protein known as melanoma differentiation associated gene-9 (mda-9)/syntenin. More than 1 million cases of skin cancer are diagnosed each year in the U.S., and melanoma is the deadliest form. With further research, the approach used by the scientists could lead to targeted therapies that stop metastasis in melanoma and potentially a broad range of additional cancers.
The study published online in the journal Cancer Research was led by Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and program co-leader of Cancer Molecular Genetics at Virginia Commonwealth University Massey Cancer Center, chairman of VCU's Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine. Fisher and his colleagues found that Raf kinase inhibitor protein (RKIP) interacted with and suppressed mda-9/syntenin. Mda-9/syntenin was originally cloned in Fisher's laboratory, and was shown in previous studies to interact with another protein, c-Src, to start a series of chemical reactions that lead to increased metastasis.
"Prior research suggests that RKIP plays a seminal role in inhibiting cancer metastasis, but, until now, the mechanisms underlying this activity were not clear," says Fisher. "In addition to providing a new target for future therapies, there is potential for using these two genes as biomarkers for monitoring melanoma development and progression."
Through their experiments, the scientists discovered that RKIP physically binds with mda-9/syntenin, and this physical interaction inhibits mda-9/syntenin expression. This finding opens the possibility of developing small molecules that mimic RKIP to be used as drugs to treat metastasis in melanoma and other cancers.
Additionally, the team found that levels of mda-9/syntenin were higher than levels of RKIP in malignant and metastatic melanoma cells while levels of RKIP were higher than levels of mda-9/syntenin in healthy melanocytes, which are the cells that produce pigment in the skin, eyes and hair. The inverse relationship between the two proteins suggests that changes in their levels of expression could be used as a diagnostic tool, enabling clinicians to track the development of the disease or gauge a patient's response to treatments.
"Our findings represent an advance in understanding the genetic mechanisms that lead to metastasis in melanoma. Prior studies have shown that levels of mda-9/syntenin are elevated in a majority of cancers, including melanoma, suggesting that our findings could be applicable for a wide range of diseases," says Fisher.
Now that the researchers have demonstrated the ability of RKIP to inhibit mda-9/syntenin-mediated metastasis, they are focusing their attention on developing small molecules imitating RKIP that could be used as new treatments for melanoma.
Virginia Commonwealth University: http://www.vcu.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Flu cases across the US can be accurately estimated using Wikipedia searches, and fluey tweets from Twitter users also give the game away
Workers who have a creative outlet outside the office are more likely to be creative problem solvers on the job, a study suggests. Oh, and they have more fun.
Scientists to grow a crop of camelina plants genetically modified to produce fish oils that could be used in health supplements Continue reading...
Kent Kiehl has been interviewing psychopaths for more than 20 years. More recently he's acquired a mobile MRI scanner and permission to scan the brains of New Mexico state prison inmates. He talked with WIRED about what's different in the brains of psychopaths and why he views psychopathy as a preventable mental disorder.
In Snakes, Sunrises, and Shakespeare, evolutionary psychology pioneer Gordon H. Orians traces the roots of today's human quirks in the minds of our ancestors
The World Health Organization says an outbreak of the deadly Ebola virus in West Africa has been linked to the deaths of more than 120 people. As of Monday, the organization recorded a total of 200 suspected or confirmed cases of Ebola, which is normally found in central or eastern Africa, in…
To see if low blood sugar sours even good relationships, scientists used an unusual tool: voodoo dolls representing spouses. As hunger levels rose, so did the number of pins.
A Beijing artist who collected a jar of air from Provence, France, sold it at auction "to question China's foul air and express dissatisfaction."
With purported activity against cardiac disease, cancer and even ageing, the pressure on resveratrol to deliver is enormous
Health workers responding to an Ebola outbreak in Guinea had no maps to go on, so they turned to the internet for help