Featured Research

from universities, journals, and other organizations

Oncogene Inhibits Tumor Suppressor To Promote Cancer: Study Links B-RAF And LKB1

Date:
February 4, 2009
Source:
Cell Press
Summary:
Scientists have uncovered an interesting connection between two important protein kinase signaling pathways that are associated with cancer. The research may direct new therapeutic strategies for multiple types of cancer.

Scientists have uncovered an interesting connection between two important protein kinase signaling pathways that are associated with cancer. The research, published 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.

The researchers include Bin Zheng, Harvard Medical School, Boston, MA; Joseph H. Jeong, Dana-Farber Cancer Institute, Boston, MA; John M. Asara, Harvard Medical School, Boston, MA; Yuan-Ying Yuan, Harvard Medical School, Boston, MA; Scott R. Granter, Brigham and Women's Hospital, Boston, MA; Lynda Chin, Dana-Farber Cancer Institute; and Lewis C. Cantley, Harvard Medical School, Boston, MA.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Oncogene Inhibits Tumor Suppressor To Promote Cancer: Study Links B-RAF And LKB1." ScienceDaily. ScienceDaily, 4 February 2009. <www.sciencedaily.com/releases/2009/01/090129122518.htm>.
Cell Press. (2009, February 4). Oncogene Inhibits Tumor Suppressor To Promote Cancer: Study Links B-RAF And LKB1. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2009/01/090129122518.htm
Cell Press. "Oncogene Inhibits Tumor Suppressor To Promote Cancer: Study Links B-RAF And LKB1." ScienceDaily. www.sciencedaily.com/releases/2009/01/090129122518.htm (accessed October 2, 2014).

Share This



More Health & Medicine News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Ebola Patient Told Hospital He Was from Liberia

Ebola Patient Told Hospital He Was from Liberia

AP (Oct. 1, 2014) The first Ebola patient diagnosed in the U.S. initially went to a Dallas emergency room last week but was sent home, despite telling a nurse that he had been in disease-ravaged West Africa, the hospital acknowledged Wednesday. (Oct. 1) Video provided by AP
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins