Related Experiment Video
Updated: May 4, 2026
10:08
Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
1.8K
P14ARF suppresses tumor-induced thrombosis by regulating the tissue factor pathway
Abdessamad Zerrouqi1, Beata Pyrzynska, Daniel J Brat
1Authors' Affiliations: Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery; Departments of Pathology and Laboratory Medicine and Hematology and Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, Georgia.
Cancer Research
|January 9, 2014
Summary
Loss of tumor suppressor P14ARF activates the clotting cascade in glioblastoma, promoting tumor necrosis. P14ARF normally prevents thrombosis by upregulating TFPI2, a clotting inhibitor.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Tumor necrosis is linked to vascular microthrombi formation and coagulation activation.
- The role of tumor suppressors in regulating thrombosis remains incompletely understood.
Purpose of the Study:
- To investigate the role of P14ARF in regulating the coagulation cascade within glioblastoma.
- To identify the molecular mechanisms by which P14ARF influences thrombosis and tumor necrosis.
Main Methods:
- Analysis of P14ARF's effect on TFPI2 expression and promoter activity.
- Investigating the signaling pathways (p53, c-JUN, SP1, JNK) involved in P14ARF-mediated TFPI2 regulation.
- Assessing the impact of P14ARF on plasma clotting activation in glioblastoma cells.
Main Results:
- Loss of P14ARF in glioblastoma promotes activation of the clotting cascade.
- P14ARF transcriptionally upregulates TFPI2, a Kunitz-type serine protease that inhibits thrombosis.
- P14ARF-mediated TFPI2 activation occurs independently of p53, involving c-JUN, SP1, and JNK signaling.
Conclusions:
- P14ARF plays a critical role in preventing vascular microthrombosis initiated by glioma cells.
- Targeting the P14ARF-TFPI2 pathway may offer a therapeutic strategy against aggressive, necrotic glioblastoma.
Related Concept Videos
02:23Abnormal Proliferation
4.0K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
2.6K
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
2.6K
01:12Loss of Tumor Suppressor Gene Functions
4.9K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
01:12Loss of Tumor Suppressor Gene Functions
1.7K
1.7K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
8.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.3K
01:24Regulation of Angiogenesis and Blood Supply
2.9K
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...
2.9K