Frataxin participates to the hypoxia-induced response in tumors

I Guccini1, D Serio, I Condò

  • 1Department of Experimental Medicine and Biochemical Sciences, Laboratory of Signal Transduction, University Tor Vergata, Rome, Italy.

Cell Death & Disease
|March 4, 2011
PubMed

Insights

Frataxin protein, crucial for cell survival, is upregulated in tumor cells during hypoxia. This finding reveals frataxin

Area of Science:

  • Molecular biology
  • Cancer research
  • Cellular stress response

Background:

  • Frataxin deficiency causes Friedreich's ataxia.
  • Frataxin's dual role as a tumor suppressor and protector of tumor cells against stress is paradoxical.
  • The molecular mechanisms underlying frataxin's function in tumor cells remain unclear.

Purpose of the Study:

  • To investigate the pathways by which frataxin enhances stress resistance in tumor cells.
  • To elucidate the role of frataxin in the tumor microenvironment, particularly under hypoxic conditions.

Main Methods:

  • Analysis of frataxin expression in tumor cell lines under hypoxic stress.
  • Investigation of the dependence of frataxin upregulation on hypoxia-inducible factors (HIFs).
  • Assessment of frataxin's modulation of tumor suppressor p53 activation.
  • Validation of frataxin levels in human tumors in vivo.

Main Results:

  • Frataxin expression is upregulated in tumor cells in response to hypoxia.
  • Hypoxia-induced frataxin upregulation is mediated by hypoxia-inducible factors.
  • Frataxin influences the activation of the tumor suppressor p53.
  • Frataxin levels are elevated in human tumors.

Conclusions:

  • Frataxin plays a significant role in the hypoxia-induced stress response within tumors.
  • The findings suggest frataxin is involved in tumor cell survival and progression.
  • Modulating frataxin expression may represent a therapeutic strategy for cancer.

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Hypoxia01:23

Hypoxia

Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...