Featured Research

from universities, journals, and other organizations

Protein 'Switch' Suppresses Skin Cancer Development

Date:
September 10, 2008
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
The protein IKKalpha (IKK±) regulates the cell cycle of keratinocytes and plays a key role in keeping these specialized skin cells from becoming malignant, researchers report in Cancer Cell.

The protein IKKalpha (IKKα) regulates the cell cycle of keratinocytes and plays a key role in keeping these specialized skin cells from becoming malignant, researchers at The University of Texas M. D. Anderson Cancer Center report in the Sept. 9 issue of Cancer Cell.

"We have shown that IKKα acts as a sentry, monitoring and, when necessary, halting proliferation of these important cells. In the first mouse model of its kind, we also found that deleting IKKα spontaneously induced squamous cell carcinomas by activating the epidermal growth factor receptor pathway," said senior author Yinling Hu, Ph.D., assistant professor in M. D. Anderson's Department of Carcinogenesis at the Science Park - Research Division in Smithville, Texas. "These results provide new therapeutic targets for prevention of skin cancer."

Keratinocytes originate in the basal layer of the epidermis to replace skin cells at the surface that have been shed. As keratinocytes gradually move up through the skin layers, they differentiate and eventually form the top layer of the skin, which is composed of squamous cells. The cycle ends through terminal differentiation, in which cells lose their ability to reproduce by dividing in two. They eventually die.

Hu and colleagues reported in research last year that a reduction in IKKα expression promotes the development of chemically induced papillomas and carcinomas, which are benign and malignant tumors of the epithelium respectively. Epithelial cells make up the outer layers of skin and the inner linings of many organs, including the lungs and the gastrointestinal, reproductive and urinary tracts. Most cancers originate in organ epithelial cells. The researchers also demonstrated that an intact IKKα gene is required to suppress skin cancer development.

Downregulation of IKKα has been noted in a variety of human squamous cell carcinomas, including those of the skin, esophagus, lungs, and head and neck.

IKKα's role in maintaining skin homeostasis, or stability, had remained unclear because an appropriate mouse model was not available. To solve this problem, Bigang Liu, the first author, and colleagues generated mice with IKKα deletions in their keratinocytes.

In a series of experiments, Hu's group found evidence that IKKα functions as a sentry that monitors keratinocyte proliferation and then induces terminal differentiation. In one experiment, within a few days of birth, mutant mice had developed thickened and wrinkled skin and gradually showed retarded development. The researchers also found that even a low level of IKKα in the epidermis was sufficient to allow normal embryonic skin development.

The researchers examined the signaling pathways involved in overproliferation and reduced differentiation in IKKα -deficient cells. In one, they found that IKKα turns down a cellular signaling loop that activates EGFR and other growth factors previously found to regulate keratinocyte proliferation and differentiation.

Another experiment demonstrated that IKKα deletions in keratinocytes cause skin carcinomas and that inactivating EGFR reverses this process in the mutant mice. Furthermore, either inactivation of EGFR or reintroduction of IKKα inhibited excessive cell division, induced terminal differentiation, and prevented skin cancer by repressing the EGFR-driven signaling loop.

Hu's group concluded that IKKα is a switch for proliferation and differentiation and is essential to maintaining skin homeostasis, or stability, and preventing skin cancer.

"This study has revealed the importance of IKKα in maintaining skin homeostasis and in preventing skin cancer, as well as the mechanism of how IKKα acts in these processes," Hu said. "We will further investigate how IKKα deletion targets a single cancer initiation cell, which will provide new avenues to treat cancer."

Co-authors with Hu and Liu are Xiaojun Xia, Ph.D., Feng Zhu, Ph.D., Eunmi Park, Ph.D., Steve Carbajal, Kaoru Kiguchi, M.D., Ph.D., John DiGiovanni, Ph.D., and Susan Fischer, Ph.D., all of M. D. Anderson's Science Park - Research Division.

Research was funded by grants from the National Cancer Institute. Hu moved this month to the Cancer and Inflammation Program, Center for Cancer Research at the National Cancer Institute.


Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Protein 'Switch' Suppresses Skin Cancer Development." ScienceDaily. ScienceDaily, 10 September 2008. <www.sciencedaily.com/releases/2008/09/080908140100.htm>.
University of Texas M. D. Anderson Cancer Center. (2008, September 10). Protein 'Switch' Suppresses Skin Cancer Development. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2008/09/080908140100.htm
University of Texas M. D. Anderson Cancer Center. "Protein 'Switch' Suppresses Skin Cancer Development." ScienceDaily. www.sciencedaily.com/releases/2008/09/080908140100.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) — Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) — Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) — The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) — Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
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:
from the past week

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