Featured Research

from universities, journals, and other organizations

FOXO Factor Promotes Survival Of Oxygen-deprived Cancer Cells

Date:
January 4, 2008
Source:
Cell Press
Summary:
Scientists report that an evolutionarily conserved transcription factor may have both positive and negative effects on the growth of tumors, depending on whether or not the tumor cells have enough oxygen. The research provides critical new information about how normal cells and cancer cells survive under stress.

Scientists report that an evolutionarily conserved transcription factor may have both positive and negative effects on the growth of tumors, depending on whether or not the tumor cells have enough oxygen. The research provides critical new information about how normal cells and cancer cells survive under stress.

Dividing tumor cells are often deprived of oxygen as a result of their rapid expansion or aberrant blood vessels. Response to stressful low oxygen conditions, known as hypoxia, involves expression of several genes that enable cells to adapt to the oxygen deficit. This response is primarily mediated by the hypoxia-inducible transcription factors, HIF1 and HIF2.

HIF proteins play a key role in hypoxic tumor development and are often associated with poor patient prognosis. Hypoxic tumor cells exhibit decreased sensitivity to radiation and chemotherapy, and increased potential for invasion and metastasis. Interestingly, recent research findings have also revealed an anti-cancer role for HIF1 that is mediated by the initiation of programmed cell death, called apoptosis, in response to severe hypoxic stress. Although HIF1 has been linked to several pro-apoptotic target genes, specific mechanisms that regulate this particular function of HIF1 are not well understood.

Dr. Tak W. Mak from the Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital in Toronto and colleagues found that hypoxia stimulates an HIF1-dependent increase in a protein called FOXO3a. FOXO transcription factors are evolutionarily conserved proteins that are critical regulators of cell survival under stressful conditions. Recently, FOXO proteins have also been shown to act as tumor suppressors.

Dr. Mak's group observed that under hypoxic conditions, FOXO3a inhibited HIF-1 induced apoptosis in normal cells and breast cancer cells by stimulating the transcription of the HIF1 target gene CITED2. Activation of CITED2, known to exert a negative influence on HIF1 activity, resulted in reduced expression of pro-apoptotic HIF1 target genes.

"Our results reveal a pro-survival role for FOXO3a in normal cells and cancer cells that are adapting to hypoxic stress," explains Dr. Mak. "Targeting of this pathway may benefit cancer treatment. Tumorigenesis could possibly be inhibited by either very high levels of FOXO3a/CITED2 activity that would cause complete inhibition of HIF1 or very low levels that would permit HIF1- induced apoptosis under hypoxic stress."

This research is published by Cell Press in the December 28th issue of Molecular Cell.

The researchers include Walbert J. Bakker, Isaac S. Harris, and Tak W. Mak, all of the Campbell Family Institute for Breast Cancer Research, University Health Network, Ontario Cancer Institute and Princess Margaret Hospital, Toronto, ON, Canada.


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. "FOXO Factor Promotes Survival Of Oxygen-deprived Cancer Cells." ScienceDaily. ScienceDaily, 4 January 2008. <www.sciencedaily.com/releases/2007/12/071227184104.htm>.
Cell Press. (2008, January 4). FOXO Factor Promotes Survival Of Oxygen-deprived Cancer Cells. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2007/12/071227184104.htm
Cell Press. "FOXO Factor Promotes Survival Of Oxygen-deprived Cancer Cells." ScienceDaily. www.sciencedaily.com/releases/2007/12/071227184104.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) 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:
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