Navigation Links
Sanford-Burnham researchers find molecular switch that allows melanoma to resist therapy
Date:2/2/2012

LA JOLLA, Calif. -- The National Cancer Institute (NCI) estimates that as many as one in 51 men and women will be diagnosed with melanomathe deadliest form of skin cancerat some point during their lifetimes. A research team led by Ze'ev Ronai, Ph.D. at Sanford-Burnham Medical Research Institute (Sanford-Burnham) is working to unravel the molecular mechanisms underlying the development and progression of this disease in hopes of improving prevention and treatment strategies. To do this, Ronai's laboratory has been studying a protein named Activating Transcription Factor 2 (ATF2), which is associated with poor prognosis in melanoma. ATF2 is a two-faced proteinin melanoma cells, it's oncogenic, or cancer-causing, while in non-malignant types of skin cancers, it acts as a tumor suppressor. In a paper published February 3 in the journal Cell, the team identified a molecular switch that controls ATF2's dual functions. This switch is controlled by protein kinase Cε (PKCε), which disables ATF2's tumor-suppressing activities, sensitizing cells to chemotherapy; instead, ATF2's tumor-promoting activity is enhanced. The team also found that high levels of PKCε in melanoma are associated with poor prognosis.

"PKCε is the culprit behind melanoma's 'oncogenic addiction,'" said Ronai, associate director of the Sanford-Burnham's NCI-designated Cancer Center and senior author of the study. "ATF2 is normally a 'good guy.' But when there is too much PKCεas in malignant melanomaATF2 becomes an oncogene, promoting tumor development."

In this study, Ronai and lead author Eric Lau, Ph.D., a postdoctoral researcher in his lab, found that PKCε's malignant power is in its ability to direct ATF2's location and activity within a cell. In a normal cell, PKCε modifies ATF2, keeping it in the nucleus, where it turns genes on and off and helps repair damaged DNA. When the cell experiences exposure to toxicity or stress (radiation, for example), PKCε backs off and ATF2 is able to move out of the nucleus and to the mitochondria, the part of the cell that generates energy and helps control cellular life and death. When it gets there, ATF2 helps to set the cell on a death coursea safeguard cells use to prevent errors that often make them cancerous.

PKCε levels are abnormally high in melanoma, and more PKCε means more ATF2 stuck in the nucleus, where it can't help the cells to die. Instead, in the nucleus, ATF2 promotes cellular survival and thus contributes to tumor development.

"We found that melanoma patients with high PKCε levels in their primary tumors were more likely to experience shorter survival times," said Lau. "This finding is consistent with earlier analyses of human melanoma tumors that showed a similar correlation between increased nuclear ATF2 and poor clinical outcome."

The Ronai laboratory, in collaboration with Sanford-Burnham's Conrad Prebys Center for Chemical Genomics, is currently searching for small molecules that help release ATF2 from PKCε's grip, thereby resuming ATF2's ability to promote cell death when needed. Since such an approach will effectively kill melanoma cells, it is expected to offer new therapeutic options for melanoma, and possibly other tumors with high PKCε levels.

"This work has clear potential for translation from a basic laboratory discovery to a melanoma therapy," said Michael Jackson, Ph.D., vice president of drug discovery and development at Sanford-Burnham. "We are excited to begin the screening process to identify a new class of drugs to treat cancer."


'/>"/>
Contact: Heather Buschman, Ph.D.
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert  

Related medicine news :

1. Scripps Health and Sanford-Burnham to collaborate to advance new cancer treatments
2. Dr. Kristiina Vuori Promoted to President of Sanford-Burnham Medical Research Institute
3. Dana-Farber and Sanford-Burnham Institute license flu-targeting antibodies to Genentech and Roche
4. Researchers Spot Potential Bile Duct Cancer Drug Targets
5. Georgetown Lombardi researchers present new findings on head & neck cancers
6. Researchers discover method to unravel malarias genetic secrets
7. Researchers quantify muscle soreness
8. Georgetown professor applauds decision of researchers to temporarily halt research on H5N1
9. Health benefits of exercise may depend on cellular degradation, UT Southwestern researchers report
10. Autism redefined: Yale researchers study impact of proposed diagnostic criteria
11. University of Tennessee researchers develop comprehensive, accessible vision testing device
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Sanford-Burnham researchers find molecular switch that allows melanoma to resist therapy
(Date:6/27/2016)... ... June 27, 2016 , ... "FCPX editors can now reveal their ... Cut Pro X," said Christina Austin - CEO of Pixel Film Studios. , ... Pro X users can now reveal the media of their split screens with ...
(Date:6/26/2016)... ... ... Quality metrics are proliferating in cancer care, and are derived from many ... the beholder, according to experts who offered insights and commentary in the current issue ... the full issue, click here . , For the American Society of Clinical ...
(Date:6/26/2016)... ... June 26, 2016 , ... ... have been diagnosed with endometriosis. These women need a treatment plan to not ... comprehensive approach that can help for preservation of fertility and ultimately achieving a ...
(Date:6/25/2016)... ... 25, 2016 , ... First Choice Emergency Room , the largest network ... the Medical Director of its new Mesquite-Samuell Farm facility. , “We are pleased ... location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. ...
(Date:6/24/2016)... ... 2016 , ... A recent article published June 14 on E ... goes on to state that individuals are now more comfortable seeking to undergo not ... as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills Physicians ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016  Guerbet announced today that ... Supplier Horizon Award . One of ... was recognized for its support of Premier members through ... clinical excellence, and commitment to lower costs. ... this recognition of our outstanding customer service from Premier," ...
(Date:6/23/2016)... 2016 Research and Markets has ... Global Analysis (United States, China, Japan, Brazil, United Kingdom, ... their offering. Surgical ... business planners, provides surgical procedure volume data in a ... an in-depth analysis of growth drivers and inhibitors, including ...
(Date:6/23/2016)... , June 23, 2016 The ... it continues to present great opportunities to investors. Stock-Callers.com ... today: Intrexon Corp. (NYSE: XON ), Vertex ... Inc. (NASDAQ: ARNA ), and Regeneron Pharmaceuticals ... these stocks and receive your complimentary trade alerts at: ...
Breaking Medicine Technology: