Navigation Links
FOXO factor promotes survival of oxygen-deprived cancer cells
Date:12/27/2007

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, published by Cell Press in the December 28th issue of Molecular Cell, 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. Maks 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.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
2. Study, meta-analysis examine factors associated with death from heatstroke
3. New Alzheimers findings: High stress and genetic risk factor lead to increased memory decline
4. Discovery suggests location of genes for breast density, a strong risk factor for breast cancer
5. PA Health Department Survey Shows Impact of Income, Gender, Other Factors on Health and Access to Health Care
6. Researchers genetically engineer micro-organisms into tiny factories
7. Study Downgrades Gene as Heart Risk Factor
8. Severe heart defect likely caused by genetic factors
9. A Chinese medicine compound has satisfactory anti-cancer effects on hepatocellular carcinoma
10. Aggressively Treating Cardiac Risk Factors May Reverse Ischemia
11. New peptide communication factor enabling bacteria to talk to each other discovered
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... OBISPO, Calif. (PRWEB) , ... October 13, 2017 , ... ... or dementia. However, many long-term care insurance companies have a waiver for care if ... the 90-day elimination period, when the family pays for care, is often waived, so ...
(Date:10/13/2017)... NJ (PRWEB) , ... October 13, 2017 , ... Global ... at scenic Alexandria Park in Milford, NJ. This free event, sponsored by Global ... physical activity. The fun run is geared towards children of all ages; it ...
(Date:10/13/2017)... ... October 13, 2017 , ... ... Software Development, has been awarded a contract by the Center for Medicare and ... aims to accelerate the enterprise use of Agile methodologies in a consistent and ...
(Date:10/12/2017)... Del. (PRWEB) , ... October 12, 2017 , ... ... and advisory services for healthcare compliance program management, will showcase a range of ... National Association for Assisted Living (NCAL) Convention and Expo to be held October ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... meet the demand of today’s consumer and regulatory authorities worldwide. From Children’s to ... and tested to meet the highest standard. , These products are also: ...
Breaking Medicine News(10 mins):
(Date:10/4/2017)... 2017  According to the Centers for Disease Control and Prevention (CDC), ... PhysicianOne Urgent Care is helping communities across Massachusetts , ... by offering no-cost* flu shots through the end of the month. ... insurance regulations. ... get a flu shot is by the end of October, according to ...
(Date:10/2/2017)... Halo Labs announces the European launch of their new ... at MIBio 2017 in Cambridge, U.K on ... in biopharmaceutical samples with unprecedented speed and sensitivity while using far ... Membrane Imaging. ... particle analysis system ...
(Date:9/27/2017)... and NEW YORK , Sept. 27, 2017 /PRNewswire/ ... health and big data solutions, today announced that its MyDario product is ... your local TV listings for when The Dr. Oz Show airs in ... The nine-time ... month. ...
Breaking Medicine Technology: