TNF-related apoptosis-inducing ligand signaling pathway and hematopoietic malignancies.
- Author:
Jun QIAN
1
;
Zi-Xing CHEN
Author Information
1. Leukemia Research Unit, The First Affiliated Hospital, Suzhou University, Suzhou 215006, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis Regulatory Proteins;
Hematologic Neoplasms;
etiology;
therapy;
Humans;
Membrane Glycoproteins;
physiology;
Mutation;
Receptors, TNF-Related Apoptosis-Inducing Ligand;
Receptors, Tumor Necrosis Factor;
genetics;
physiology;
Signal Transduction;
TNF-Related Apoptosis-Inducing Ligand;
Tumor Necrosis Factor-alpha;
physiology
- From:
Journal of Experimental Hematology
2002;10(5):472-477
- CountryChina
- Language:Chinese
-
Abstract:
TNF-related apoptosis-inducing ligand (TRAIL) is a newly identified member of the tumor necrosis factor (TNF) family. TRAIL induces apoptosis by activating caspase cascades, stimulating a loss of mitochondrial membrane potential (Delta Psim) and cytochrome C release in the FADD/caspase-8 dependent pathway. However, TRAIL can also trigger transcriptional activations of the pro-oncogene of c-fos, JNK, and NF-kappaB by other signaling pathways downstream of FADD/caspase-8. MAPK/ERK activation has a dominant protecting effect over apoptotic signaling from the death receptors. The functional expression of TRAIL by leukemic cells may be involved in tumor cells evasion of immunosurveillance. Somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some tumors. TRAIL can induce apoptosis on various continuous transformed cell lines and primary tumor cells, including several of hematopoietic origin, displaying minimal toxic effects on normal tissues. Because of the abilities of induction of both cytotoxic (apoptosis) and cytostatic (cell cycle perturbation) effects on the leukemic cells, TRAIL is currently considered as a potential(co) therapeutic drug against tumors.
