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:12/7/2016)... ... 07, 2016 , ... “The Road To Restoration”: an informative and enlightening ... hour a week showing of hands. “The Road To Restoration” is the creation of ... familiar with the brass ring that you could reach out for, and grab, on ...
(Date:12/7/2016)... ... 07, 2016 , ... “Fred Rides a Train” allows readers to tag along ... “Fred Rides a Train” is the creation of published author, Janet Morrison, who has ... in Michigan. The "Fred, the Dog" series is her first attempt at writing for ...
(Date:12/7/2016)... WI (PRWEB) , ... December 07, 2016 , ... ... Labs, was honored to present at the International Probiotic Association’s Washington DC workshop ... and government regulators to engage in dialog regarding probiotic dietary supplement regulations. ...
(Date:12/6/2016)... ... December 06, 2016 , ... People ... can be seen on a type of MRI, according to a study appearing ... of the central nervous system characterized by tremors or trembling and stiffness in ...
(Date:12/6/2016)... ... December 06, 2016 , ... Individuals who seek to reduce ... drinking more water or limiting their exposure to the sun, according to a November ... group Beverly Hills Physicians (BHP) notes that, while preventive measures to help keep ourselves ...
Breaking Medicine News(10 mins):
(Date:12/7/2016)... , Dec. 7, 2016  Varian Medical Systems (NYSE: ... its previously announced plans to separate its Imaging Components ... a tax-free distribution to Varian stockholders of common stock ... that will hold the Imaging Components business.  As part ... executed by the end of January 2017, Varian will ...
(Date:12/7/2016)... , Dec. 7, 2016 Boehringer ... trial in patients with unresectable malignant pleural mesothelioma ... (PFS). The data, presented at the 17 th ... Vienna , showed nintedanib plus ... placebo plus pemetrexed/cisplatin, with a significantly improved PFS ...
(Date:12/7/2016)... , Dec. 7, 2016  Organovo Holdings, Inc. ... biology company focused on delivering scientific and medical ... that Chairman and Chief Executive Officer Keith ... on Wednesday, December 14, 2016 at 1:00 p.m. ... are not yet familiar with the Company, an ...
Breaking Medicine Technology: