Navigation Links
Oncogene inhibits tumor suppressor to promote cancer: Study links B-RAF and LKB1
Date:1/29/2009

Scientists have uncovered an interesting connection between two important protein kinase signaling pathways that are associated with cancer. The research, published by Cell Press in the January 30th issue of the journal Molecular Cell, may direct new therapeutic strategies for multiple types of cancer.

The protein kinase LKB1 is a known tumor suppressor and the LKB1-AMPK signaling pathway couples energy metabolism with cell growth, proliferation and survival. "Mutations in LKB1 are not frequent in human cancers and it is not clear how tumor cells suppress the signaling pathway to gain growth advantage under conditions of energy stress (common in cancer cells)," explains senior study author Dr. Lewis C. Cantley from Beth Israel Deaconess Medical Center and Harvard Medical School.

Dr. Cantley and colleagues, including Dr. Bin Zheng, designed a study to investigate the molecular mechanisms associated with suppression of the LKB1-AMPK pathway in tumor cells. The researchers used malignant melanoma cells that often have a mutation called "V600E" in the RAF protein B-RAF. The RAF-MEK-ERK pathway is well established as a key regulator of cell growth, proliferation, differentiation and survival.

Mutations in the RAF kinase B-RAF have been found in many types of human cancer but, while oncogenic B-RAF V600E has been linked with tumor induction, growth, maintenance and progression, the specific molecular mechanisms have not been identified. Dr. Cantley's group found that melanoma cells with the B-RAF V600E mutation had impaired AMPK activation and that inhibition of B-RAF signaling activated AMPK.

The researchers went on to show that LKB1 was phosphorylated by two kinases that are downstream of B-RAF, ERK and Rsk. The phosphorylation of LKB1 interfered with the ability of LKB1 to bind and activate AMPK. Importantly, expression of mutant LKB1 that could not be phosphorylated resulted in activation of AMPK and an inhibition of melanoma cell proliferation.

"Taken together, our results provide a molecular linkage between the LKLB1-AMPK and the RAF-MEK-ERK pathways and suggest that suppression of LKB1 function by B-RAF V600E plays an important role in B-RAF V600E-driven tumorigenesis," says Dr. Zheng. "It's conceivable that tumor cells must turn off the LKB1-AMPK signaling pathway to gain a growth advantage under conditions of energy stress."

Given that B-RAF mutation and loss of LKB1 are associated with multiple types of cancer, the work is likely to have a significant clinical impact. "Further understanding of how the intriguing molecular linkage between LKB1-AMPK and RAF-MEK-ERK functions in tumorigenesis could potentially provide great therapeutic opportunities for cancer treatment," offers Dr. Cantley.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. MicroRNA controls expression of oncogenes
2. Colon Cancer Oncogene Discovered
3. Blocking Oncogene Can Stop Spread of Ovarian Cancer
4. Helicobacter pylori inhibits intercellular communication of cultured gastric cells
5. Blocking protein kills prostate cancer cells, inhibits tumor growth, Jefferson scientists find
6. Embryonic Stem Cell Protein Inhibits Melanoma
7. Penn scientists find a protein that inhibits Ebola from reaching out to infect neighboring cells
8. Ingredient found in green tea significantly inhibits breast cancer growth in female mice
9. Calorie restriction limits Calorie restriction inhibits, obesity fuels development of epithelial can
10. Calorie restriction inhibits, obesity fuels development of epithelial cancers
11. Grapefruit Compound Inhibits Hepatitis C Virus
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... ... April 28, 2016 , ... In 2011, TIME magazine named Herr ... field of biomechatronics, technology that marries human physiology with electromechanics. He continues that work ... also the Founder of BionX , a leader in the field of prosthetic ...
(Date:4/28/2016)... ... April 28, 2016 , ... One way to ignore solid evidence is ... true. But we toss the baby out with the bathwater when we ignore all ... identifying higher-quality studies and otherwise making better use of education policy research. , “When ...
(Date:4/28/2016)... ... April 28, 2016 , ... Anzu®, ... announced a new Residency Education & Collaboration Platform for hospitals and medical ... and a host of collaboration tools designed to improve patient outcomes through ...
(Date:4/28/2016)... ... April 28, 2016 , ... Accreditation Commission for Health Care ... (COPA) to develop a comprehensive Specialty Pharmacy Accreditation with Distinction in Oncology. This ... ACHC provides a wide range of pharmacy accreditation services that assess the business ...
(Date:4/28/2016)... MO (PRWEB) , ... April 28, 2016 , ... Denise McCormick Baich had written poetry ... 2009 the poetry arrived again much like a tsunami and took on a more spiritual ... to her encouraged her to do more with it than just file it away. Friends ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)...  Bayer Animal Health today announced that ... of Florida College of Veterinary Medicine, is the ... Award (BECA). Brittany was selected from entries representing ... of $70,000 in scholarship funds through the 2016 ... provided a total of $232,500 in scholarship awards ...
(Date:4/27/2016)... DUBLIN , April 27, 2016 /PRNewswire/ ... the addition of the  "Global Anesthesia Disposables ... (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO ) ,The global ... at a CAGR of 4.03% during the ... are a major threat to patients, safety. ...
(Date:4/27/2016)... 2016 Global  urinalysis market ... by 2022, according to a new report by ... http://photos.prnewswire.com/prnh/20150105/723757 ) , Automation ... and accuracy delivered by the new generation urinalysis ... urinalysis instruments and consumables. For instance, the automatic ...
Breaking Medicine Technology: