Related Experiment Video
Updated: Aug 5, 2026
07:23
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
CLK3 regulates tumor angiogenesis by modulating HIF1α ubiquitination
Jing Shen1, Wen Zhang2, Zhiqiang Chu2
1Department of Scientific Research, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, PR China.
Cancer Gene Therapy
|July 27, 2026
Summary
CDC-like kinase 3 (CLK3) promotes tumor angiogenesis by stabilizing hypoxia-inducible factor 1-alpha (HIF1α). Targeting CLK3 offers a potential therapeutic strategy for colorectal cancer, addressing limitations in current angiogenesis inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tumor angiogenesis is crucial for cancer progression but faces therapeutic limitations.
- Developing novel angiogenesis inhibitors and identifying reliable biomarkers are essential.
Purpose of the Study:
- To investigate the role of CDC-like kinase 3 (CLK3) in tumor angiogenesis.
- To elucidate the molecular mechanisms underlying CLK3's function in angiogenesis.
Main Methods:
- Bioinformatic analysis of clinical datasets for CLK3 expression.
- In vitro and in vivo experiments (overexpression and knockout models).
- Mechanistic studies involving protein-protein interactions, degradation pathways, and phosphorylation.
Main Results:
- CLK3 expression correlates with angiogenesis pathways in colorectal cancer.
- CLK3 overexpression promotes, while CLK3 knockout inhibits, tumor angiogenesis.
- CLK3 stabilizes hypoxia-inducible factor 1-alpha (HIF1α) by preventing degradation and promoting phosphorylation.
- CLK3-mediated angiogenesis is dependent on HIF1α.
Conclusions:
- CLK3 plays a significant role in regulating tumor angiogenesis.
- Targeting CLK3 presents a promising therapeutic strategy for colorectal 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...
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...
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...