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:10/13/2017)... Vegas, Nevada (PRWEB) , ... October 13, 2017 , ... ... 7® Hemp CBD Oil utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD ... dose required and providing a CBD form that can be easily incorporated into liquid ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... The Visiting ... Day Market. Featuring a collection of specialty vendors and unique items from across the ... and quality-focused health and wellness services offered by the VNA. The boutique will ...
(Date:10/13/2017)... ... October 13, 2017 , ... Coveros, a ... has been awarded a contract by the Center for Medicare and Medicaid Services ... accelerate the enterprise use of Agile methodologies in a consistent and high value ...
(Date:10/12/2017)... ... ... Planet Fitness, one of the largest and fastest growing franchisors and operators ... location in Covington, LA at 401 N. U.S. Highway 190, in January of 2018. ... in the Holiday Square shopping center. Its location allows it to serve both Covington ...
(Date:10/12/2017)... ... 12, 2017 , ... Information about the technology: , Otomagnetics ... enable prevention of a major side effect of chemotherapy in children. Cisplatin and ... For cisplatin, hearing loss is FDA listed on-label as a dose limiting toxicity. ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... , Oct. 12, 2017 AVACEN Medical ... the company with their  2017 New Product Innovation Award ... on extensive primary and secondary medical device market research by ... through its first-to-market OTC, drug-free pain relief product, the AVACEN ... approach to treating fibromyalgia widespread pain. ...
(Date:10/12/2017)... -- West Pharmaceutical Services, Inc. (NYSE: WST), ... administration, today announced that it will release third-quarter 2017 ... 26, 2017, and will follow with a conference call ... a.m. Eastern Time. To participate on the call, please ... is 94093362. A ...
(Date:10/11/2017)...  Caris Life Sciences ® , a leading innovator ... precision medicine, today announced that St. Jude Medical Center,s ... (POA) as its 17 th member. Through participation ... Cancer Institute will help develop standards of care and ... making cancer treatment more precise and effective. ...
Breaking Medicine Technology: