Restoring TRAIL mediated signaling in ovarian cancer cells.

Abstract

Ovarian cancer has emerged as a multifaceted and genomically complex disease. Genetic/epigenetic mutations, suppression of tumor suppressors, overexpression of oncogenes, rewiring of intracellular signaling cascades and loss of apoptosis are some of the deeply studied mechanisms. In vitro and in vivo studies have highlighted different molecular mechanisms that regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apoptosis in ovarian cancer. In this review, we bring to limelight, expansion in understanding systematical characterization of ovarian cancer cells has led to the rapid development of new drugs and treatments to target negative regulators of TRAIL mediated signaling pathway. Wide ranging synthetic and natural agents have been shown to stimulate mRNA and protein expression of death receptors. This review is compartmentalized into programmed cell death protein 4, platelet-derived growth factor signaling and miRNA control of TRAIL mediated signaling to ovarian cancer. Mapatumumab and PRO95780 have been tested for efficacy against ovarian cancer. Use of high-throughput screening assays will aid in dissecting the heterogeneity of this disease and increasing a long-term survival which might be achieved by translating rapidly accumulating information obtained from molecular and cellular studies to clinic researches.

• Authors: Ammad Ahmad Farooqi, Ilhan Yaylim, Nazlı Ezgi Ozkan, Farrukh Zaman, Talha Abdul Halim, Hsueh-Wei Chang
• Journal: Archivum immunologiae et therapiae experimentalis (Arch Immunol Ther Exp (Warsz)) Vol. 62 Issue 6 Pg. 459-74 (Dec 2014) ISSN: 1661-4917 [Electronic] Switzerland
• PMID: 25030086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Apoptosis Regulatory Proteins
• CASP8 and FADD-Like Apoptosis Regulating Protein
• CRYAB protein, human
• MicroRNAs
• NF-kappa B
• PDCD4 protein, human
• RNA-Binding Proteins
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10A protein, human
• TNFSF10 protein, human
• alpha-Crystallin B Chain
• Receptors, Platelet-Derived Growth Factor
• JNK Mitogen-Activated Protein Kinases

Topics

• Apoptosis
• Apoptosis Regulatory Proteins (genetics, metabolism)
• CASP8 and FADD-Like Apoptosis Regulating Protein (metabolism)
• Female
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System
• MicroRNAs (genetics)
• NF-kappa B (metabolism)
• Ovarian Neoplasms (metabolism, pathology, therapy)
• RNA-Binding Proteins (genetics, metabolism)
• Receptors, Platelet-Derived Growth Factor (genetics, metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Signal Transduction
• TNF-Related Apoptosis-Inducing Ligand (genetics, metabolism)
• alpha-Crystallin B Chain (genetics, metabolism)