Featured Research

from universities, journals, and other organizations

Gene inactivation drives spread of melanoma

Date:
June 11, 2012
Source:
University of North Carolina Health Care
Summary:
Scientists have demonstrated that inactivating a gene called LKB1 (or STK11) causes non-aggressive melanoma cells to become highly metastatic when tested in a variety of models using tumors from humans and mice. While scientists showed a role for LKB1 inactivation in lung cancer metastasis, the effects of LKB1 loss on melanoma spread is even more dramatic.

Why do some cancers spread rapidly to other organs and others don't metastasize? A team of UNC researchers led by Norman Sharpless, MD, have identified a key genetic switch that determines whether melanoma, a lethal skin cancer, spreads by metastasis.

Related Articles


Treating melanoma is extremely challenging. The cancer spreads rapidly and to sites in the body that are remote from the original cancer site. Melanoma is the most deadly form of skin cancer, and advanced melanoma kills more than 8600 Americans each year. It is the most common form of cancer in young adults, aged 25-29 and the incidence of people under 30 developing melanoma is increasing fast -- more than 50 percent in young women since 1980.

In a paper published June 11 in the journal Cancer Cell, a team from UNC Lineberger Comprehensive Cancer Center demonstrates that inactivating a gene called LKB1 (or STK11) causes non-aggressive melanoma cells to become highly metastatic when tested in a variety of models using tumors from humans and mice. While Sharpless and his colleagues showed a role for LKB1 inactivation in lung cancer metastasis, the effects of LKB1 loss on melanoma spread is even more dramatic.

"Although we are not totally certain how LKB1 loss promotes metastasis in multiple cancer types, one important effect is the loss of LKB1 starts a chain reaction, activating a family of proteins called SRC kinases, which are known to drive metastasis," said Sharpless, who is associate director for translational research at UNC Lineberger.

"Loss of LKB1 occurs in about 30 percent of lung cancer and 10 percent of melanoma, and ongoing studies at UNC and elsewhere will determine if these LKB1 deficient tumors have a worse prognosis. These data suggest LKB1 deficient cancers will be more likely to metastasize, and therefore more likely to be incurable."

"The work is exciting because the laboratory model reliably replicates distant metastases, helping us better understand what treatments may work for melanoma that has spread. While several targeted drugs have recently been approved by the FDA for metastatic disease, these targeted mutations don't indicate whether the disease is likely to metastasize," said Stergios Moschos, MD, clinical associate professor of hematology/oncology. Moschos works in the area of drug development for melanoma but was not involved in this research project.

Other members of the research team from UNC-Chapel Hill include Wenjin Liu, PhD; Kimberly Monahan, PhD; and Jessica Sorrentino, BS, from the department of genetics; Adam Pfefferle, BS, and Ryan Miller, MD, from the department of pathology and laboratory medicine; Keefe Chan, PhD, David Roadcap, PhD, and James Bear, PhD; from the department of cell and developmental biology; David Ollila, MD, from the division of surgical oncology and endocrine surgery; and Charles Perou, PhD, of the departments of genetics and pathology and the Carolina Genome Sciences Center. Dr. Miller, Bear, Ollila, and Perou are also members of UNC Lineberger Comprehensive Cancer Center and Dr. Bear is a Howard Hughes Medical Institute investigator.

Kwok-Kin Wong, MD PhD, from the Dana-Farber Cancer Institute and Harvard Medical School and Diego Castrillon, MD PhD, from the University of Texas Southwestern Medical Center also contributed to the finding.

The research was funded by the National Cancer Institute and the NCI's Mouse Model of Human Cancer Consortium (MMHCC), the National Institute on Aging and the National Institute of Environmental Health Sciences (all part of the National Institutes of Health.


Story Source:

The above story is based on materials provided by University of North Carolina Health Care. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wenjin Liu, KimberlyB. Monahan, AdamD. Pfefferle, Takeshi Shimamura, Jessica Sorrentino, KeefeT. Chan, DavidW. Roadcap, DavidW. Ollila, NancyE. Thomas, DiegoH. Castrillon, C.Ryan Miller, CharlesM. Perou, Kwok-Kin Wong, JamesE. Bear, NormanE. Sharpless. LKB1/STK11 Inactivation Leads to Expansion of a Prometastatic Tumor Subpopulation in Melanoma. Cancer Cell, 2012; 21 (6): 751 DOI: 10.1016/j.ccr.2012.03.048

Cite This Page:

University of North Carolina Health Care. "Gene inactivation drives spread of melanoma." ScienceDaily. ScienceDaily, 11 June 2012. <www.sciencedaily.com/releases/2012/06/120611134053.htm>.
University of North Carolina Health Care. (2012, June 11). Gene inactivation drives spread of melanoma. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2012/06/120611134053.htm
University of North Carolina Health Care. "Gene inactivation drives spread of melanoma." ScienceDaily. www.sciencedaily.com/releases/2012/06/120611134053.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
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