Nav: Home

FOXO factor promotes survival of oxygen-deprived cancer cells

December 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. 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."
-end-
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.

Cell Press

Related Cancer Cells Articles:

Cancer cells send signals boosting survival and drug resistance in other cancer cells
Researchers at University of California San Diego School of Medicine report that cancer cells appear to communicate to other cancer cells, activating an internal mechanism that boosts resistance to common chemotherapies and promotes tumor survival.
A protein that stem cells require could be a target in killing breast cancer cells
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Single gene encourages growth of intestinal stem cells, supporting 'niche' cells -- and cancer
A gene previously identified as critical for tumor growth in many human cancers also maintains intestinal stem cells and encourages the growth of cells that support them, according to results of a study led by Johns Hopkins researchers.
Prostate cancer cells grow with malfunction of cholesterol control in cells
Advanced prostate cancer and high blood cholesterol have long been known to be connected, but it has been a chicken-or-egg problem.
Immune therapy scientists discover distinct cells that block cancer-fighting immune cells
Princess Margaret Cancer Centre scientists have discovered a distinct cell population in tumours that inhibits the body's immune response to fight cancer.
New system developed that can switch on immune cells to attack cancer cells
Researchers have developed an artificial structure that mimics the cell membrane, which can switch on immune cells to attack and destroy a designated target.
Hybrid immune cells in early-stage lung cancer spur anti-tumor T cells to action
Researchers have identified a unique subset of these cells that exhibit hybrid characteristics of two immune cell types -- neutrophils and antigen-presenting cells -- in samples from early-stage human lung cancers.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Sleep hormone helps breast cancer drug kill more cancer cells
Tiny bubbles filled with the sleep hormone melatonin can make breast cancer treatment more effective, which means people need a lower dose, giving them less severe side effects.
Breast cancer tumor-initiating cells use mTOR signaling to recruit suppressor cells to promote tumor
Baylor College of Medicine researchers report a new mechanism that helps cancer cells engage myeloid-derived suppressor cells.

Related Cancer Cells Reading:

One Renegade Cell: How Cancer Begins (Science Masters Series)
by Robert A. Weinberg (Author)

Cancer research has reached a major turning point, and no one is better qualified to explain the past two deacades' dramatic leaps forward in understanding this disease than world-renowned molecular biologist Robert Weinberg, director of the Oncology Research Laboratory at the Whitehead Institute in Cambridge, Massachusetts. In One Renegade Cell, Weinberg presents a state-of-the-art account of how cancer begins and how, one day, it will be cured. View Details


Fred's Guide to Stem Cell Transplants: Patient to patient talk and walk down this cancer path not chosen
by Fred Roth (Author), Kathy Roth (Author)

Fred's Guide to Stem Cell Transplants... If You're Facing a Stem Cell Transplant-Fred Can Help! Chances are, if you are reading this, you or someone you love has cancer. Fred knows it can feel like an impossible, insurmountable challenge. He has been through two stem cell transplants. He knows what it's like to endure and survive the rough ride of diagnosis, assessing the risks, finding a donor, and dealing with the side effects. Having come out on the other side, Fred and Kathy have collected observations, ideas, suggestions, and insights to help you on your journey. Most of all, Fred's... View Details


Cancer: Basic Science and Clinical Aspects
by Craig A. Almeida (Author), Sheila A. Barry (Author)

“... Useful background information is displayed in blue boxes, and good use is made of numerous tables and diagrams... a useful book for the undergraduate medical or allied health professional...” –Oncology News, May/June 2010


This forward looking cancer biology book appeals to a wide ranging audience. Introductory chapters that provide the molecular, cellular, and genetic information needed to comprehend the material of the subsequent chapters bring unprepared students up to speed for the rest of the book and serve as a useful refresher for those with previous biology... View Details


Small Cell Lung Cancer - Treatment Options and Alternative Medicine
by Christian Vazquez (Author)

Small Cell Lung Cancer is a full crash course on the topic. We reviewed over 300 of the strongest natural agents that exist for cancer and found only 6 that have conclusive evidence for small cell lung cancer. The biggest problem is not lack of information in the world, it is the lack of time, understanding of the medical data associated with scientific research and to top it off there is so much data in so many directions between the pharmaceutical, people trying to steer you in the wrong way to make a quick dollar, the quacks of the industry and everything else imaginable where at the end... View Details


Cancer: The Outlaw Cell
by Richard LaFond (Editor)

We live in an era in which scientific information grows by the day and is so specialized that no one person can possibly absorb and kept abreast of the literature. Substantial developments in science and medicine, powered by developing technologies such as genetic sequencing, proteomics, and nanobiology, have driven cancer research forward, and a review of where we are now is desperately needed.

Cancer: The Outlaw Cell is a collection of twenty-five focused chapters written by leading researchers at the forefront of cancer research. Authors present the current state of... View Details


NCCN Guidelines for Patients®: Lung Cancer (Non-Small Cell), Version 1.2016
by National Comprehensive Cancer Network® (NCCN®) (Author)

[OFFICIAL CURRENT VERSION] From the medical leaders of 27 of the world’s most renowned cancer centers united under the National Comprehensive Cancer Network® (NCCN®), comes this essential guide to lung cancer (non-small cell lung cancer). Adapted from clinical treatment guidelines used by physicians and oncology professionals around the world, these NCCN Guidelines for Patients® are packed with the latest information, treatment innovations, and resources about the diagnosis and treatment of lung cancer. Each patient-friendly chapter prepares patients and caregivers to talk with their... View Details


The Biology of Cancer
by Robert A. Weinberg (Author)

The Biology of Cancer is a textbook for undergraduate and graduate biology students as well as medical students studying the molecular and cellular bases of cancer. The book presents the principles of cancer biology in an organized, cogent, and in-depth manner. The clarity of writing and the lucid full-color art program make the book accessible and engaging. The information unfolds through the presentation of key experiments which give readers a sense of discovery and provides insights into the conceptual foundation underlying modern cancer biology.

The Biology of... View Details


Cell War Notebooks: My Journey with Cervical Cancer
by Julie Forward DeMay (Author)

Beautifully written, heartwarming, and passionate, Cell War Notebooks draws us into a world many are familiar with. Recorded as a blog during a period of seven months, Cell War Notebooks is both a sensitive and brutally honest account of life with cancer. An essential read for people coping with the disease, and for the family and friends who support and love them, it's the deeply motivating story of a battle Julie Forward DeMay is determined to win. One of few memoirs written about cervical cancer, her inspirational journey was published for many reasons, one of which was to create a general... View Details


The Cancer Fighting Diet: Diet and Nutrition Strategies to Help Weaken Cancer Cells and Improve Treatment Results
by Dr. Johannes Coy Sc.D. (Author), Maren Franz (Author)

This book provides basic information about cancer, as well as detailed advice and a comprehensive diet plan to help fight a personal battle with cancer and significantly improve chances of a cure.

There are complex processes inside the human body and specific mechanisms that can lead to the development and spread of cancer cells. Understanding the causes for what is happening inside the body is the key to implementing the recommendations in this guide.

Using these recipes and nutritional strategies will cut dramatically down on sugar in order to deplete the strength and... View Details


Management of Stage I Non-Small Cell Lung Cancer, An Issue of Thoracic Surgery Clinics, 1e (The Clinics: Surgery)
by Rodney J. Landreneau MD (Author)

View Details

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Manipulation
We think we're the ones who control what we see, read, think and remember. But is that true? Who decides? And who should decide? This hour, TED speakers reveal just how easily we can be manipulated. Guests include design ethicist Tristan Harris, MSNBC host Ali Velshi, psychologist Elizabeth Loftus, and neuroscientist Steve Ramirez.
Now Playing: Science for the People

#444 The V-Word (Rebroadcast)
This week, we're looking at the social and biological science of female sex organs. We'll talk to Dr. Anthony Atala, director of the Wake Forest Baptist Medical Center Institute for Regenerative Medicine, about the creation and use of lab-grown vaginas. Biology professor Marie Herberstein exposes the bias against female genitalia in scientific studies. And science writer Emily Anthes tells us about the history and promising future of female condoms.