Related Experiment Video

Updated: May 11, 2026

Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells
06:15

Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells

Published on: November 19, 2016

Mitochondrial UQCRB regulates VEGFR2 signaling in endothelial cells

Hye Jin Jung1, Yonghyo Kim, Junghwa Chang

  • 1Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, South Korea.

Journal of Molecular Medicine (Berlin, Germany)
|May 28, 2013
PubMed
Abstract

Insights

Mitochondrial ubiquinol-cytochrome c reductase binding protein (UQCRB) boosts vascular endothelial growth factor receptor 2 (VEGFR2) signaling via reactive oxygen species (ROS). Inhibiting UQCRB with terpestacin suppresses tumor angiogenesis, offering a potential new cancer therapy.

Area of Science:

  • Mitochondrial biology
  • Cancer research
  • Angiogenesis signaling

Background:

  • Vascular endothelial growth factor (VEGF) signaling is crucial for tumor angiogenesis and a target for cancer therapy.
  • Previous studies indicated that targeting ubiquinol-cytochrome c reductase binding protein (UQCRB) in tumor cells inhibits tumor angiogenesis.
  • The precise mechanism of UQCRB's role in angiogenesis remained unclear.

Purpose of the Study:

  • To elucidate the mechanism by which UQCRB influences angiogenesis in endothelial cells (ECs).
  • To investigate the potential of UQCRB inhibition as a therapeutic strategy for cancer by targeting angiogenesis.

Main Methods:

  • Demonstrated UQCRB's role in enhancing VEGF receptor type 2 (VEGFR2) signaling in ECs.
  • Assessed the impact of terpestacin, a UQCRB inhibitor, on mitochondrial reactive oxygen species (ROS) and VEGFR2 signaling.
  • Evaluated the efficacy of terpestacin, alone and in combination with bevacizumab, in suppressing angiogenesis in vitro and in vivo.

Main Results:

  • UQCRB was found to enhance VEGFR2 signaling in ECs by increasing mitochondrial ROS production.
  • Terpestacin effectively blocked mitochondrial ROS-mediated VEGFR2 signaling pathways in ECs.
  • Terpestacin suppressed VEGF-dependent angiogenesis in vitro and in vivo.
  • Combined treatment with terpestacin and bevacizumab showed additive inhibition of tumor-induced angiogenesis.

Conclusions:

  • Mitochondrial UQCRB positively regulates VEGFR2 signaling in ECs through ROS production.
  • Inhibiting UQCRB with small molecules like terpestacin offers a novel approach to block angiogenesis.
  • Targeting UQCRB presents a potential new therapeutic strategy for human cancers by disrupting tumor angiogenesis.

More Related Videos

Mitochondrial Respiration Quantification in Yeast Whole Cells07:15

Mitochondrial Respiration Quantification in Yeast Whole Cells

Published on: November 8, 2024

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

Related Concept Videos

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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/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...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...