Related Experiment Video
Updated: Jun 9, 2026
09:17
Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
Published on: August 2, 2018
Actin-sequestering protein, thymosin beta-4, is a novel hypoxia responsive regulator
Eun-Yi Moon1, Yun-Sun Im, Yun-Kyoung Ryu
1Department of Bioscience and Biotechnology, Sejong University, Seoul, Korea. eunyimoon@sejong.ac.kr
Clinical & Experimental Metastasis
|September 8, 2010
Summary
Hypoxia induces thymosin beta-4 (TB4) expression, promoting tumor cell migration, angiogenesis, and metastasis. Inhibiting TB4 reduces these effects, suggesting TB4 is a key regulator in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Angiogenesis, driven by factors like VEGF, supports tumor growth and metastasis.
- Thymosin beta-4 (TB4) is an actin-sequestering protein involved in cytoskeletal dynamics.
- Hypoxia in tumors can induce molecular changes that promote cancer progression.
Purpose of the Study:
- To investigate the role of hypoxia-induced thymosin beta-4 (TB4) expression in melanoma cell angiogenesis and metastasis.
- To determine if TB4 mediates tumor cell migration and invasion under hypoxic conditions.
- To explore the relationship between TB4, HIF-1α stabilization, and VEGF expression in hypoxia.
Main Methods:
- Assessing TB4 expression in B16F10 melanoma cells under hypoxia.
- Utilizing TB4-transgenic (Tg) mice and wildtype littermates for comparative analysis.
- Employing wound healing assays to measure in vitro tumor cell migration.
- Using lentiviral shRNA to inhibit TB4 expression in B16F10 cells.
- Analyzing HIF-1α stabilization and VEGF isoform expression.
Main Results:
- Hypoxia increased TB4 expression in B16F10 cells time-dependently.
- TB4-Tg mice showed increased angiogenesis and HIF-1α expression compared to wildtype mice.
- Hypoxia enhanced B16F10 cell migration, which was reduced by TB4 inhibition.
- TB4 inhibition decreased hypoxia-induced HIF-1α stabilization and VEGF expression.
- TB4-Tg mice exhibited increased tumor growth and lung metastasis counts.
Conclusions:
- Hypoxia induces tumor cell migration and metastasis through TB4 expression-dependent HIF-1α stabilization.
- TB4 acts as a hypoxia-responsive regulator controlling tumor cell migration in angiogenesis and metastasis.
- Targeting TB4 may offer a therapeutic strategy to inhibit tumor progression.
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...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:23Hypoxia
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...
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...