Related Experiment Video
Updated: Jun 6, 2026
09:33
Preparation Of Neovascular Tissues from Human Glioma Tissues for Quantitative Proteomics Analysis of Tumor Angiogenesis
Published on: March 20, 2026
Pyruvate promotes tumor angiogenesis through HIF-1-dependent PAI-1 expression
Seung-Youn Jung1, Hyun Seok Song, Shi-Young Park
1Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735, Republic of Korea.
International Journal of Oncology
|December 7, 2010
Summary
Pyruvate, a byproduct of cancer cell metabolism, promotes tumor angiogenesis by upregulating plasminogen activator inhibitor-1 (PAI-1). This occurs via stabilization of hypoxia-inducible factor-1α (HIF-1α), suggesting PAI-1 as a key factor in pyruvate-driven tumor growth.
Area of Science:
- Biochemistry
- Cancer Biology
- Molecular Oncology
Background:
- Cancer cells preferentially utilize glycolysis, producing pyruvate.
- Pyruvate accumulation in cancer cells has been linked to endothelial cell activation and angiogenesis.
- The specific role of pyruvate in tumor cell-mediated angiogenesis requires further investigation.
Purpose of the Study:
- To investigate the angiogenic potential of pyruvate within tumor cells.
- To identify molecular mediators of pyruvate-induced angiogenesis in cancer.
Main Methods:
- Analysis of gene expression changes induced by pyruvate in cancer cells.
- Assessment of the pro-angiogenic activity of pyruvate and its downstream effectors.
- Investigation of the role of hypoxia-inducible factor-1α (HIF-1α) in pyruvate-mediated gene regulation.
Main Results:
- Pyruvate significantly upregulates the expression of plasminogen activator inhibitor-1 (PAI-1) in cancer cells.
- PAI-1 exhibits pro-angiogenic activity, which can be neutralized by specific antibodies.
- Pyruvate stabilizes hypoxia-inducible factor-1α (HIF-1α), facilitating PAI-1 transcription via direct promoter binding.
Conclusions:
- Pyruvate can stimulate angiogenic activity in cancer cells, even under normoxic conditions.
- PAI-1 emerges as a critical pro-angiogenic factor in pyruvate-induced angiogenesis.
- Targeting the pyruvate-PAI-1-HIF-1α axis may offer therapeutic strategies for cancer treatment.
Related Concept Videos
01:24Regulation 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...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
03:03mTOR 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...
The mTOR pathway or the...
03:03mTOR 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...
The mTOR pathway or the...
02:53Adaptive 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,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:10Mechanism of Angiogenesis
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...