mda-7 (IL-24): signaling and functional roles.
One hallmark of neoplasia is abnormal differentiation. Induction of differentiation, by chemical or biological methods, provides a possible therapeutic intervention. "Differentiation therapy" is well documented in several model systems. These include melanoma, in which treatment with interferon-beta and the protein kinase C activator mezerein induces irreversible growth arrest and terminal differentiation culminating in programmed cell death. Subtraction hybridization between terminally differentiated and untreated melanoma cells identified melanoma differentiation-associated gene-7 (mda-7), which is selectively induced during the process of melanoma terminal differentiation. Since its identification seven years ago, mda-7 has been the object of intense focus because of its unique biological properties. Firstly, mda-7 is a secreted protein having cytokine-like properties and belonging to the IL-10 cytokine family. Based on this consideration, mda-7 was renamed IL-24. Secondly if delivered by means of an adenoviral vector, mda-7 induces selective apoptosis in cancer cells of diverse origin, while sparing their normal cellular counterparts. As such, mda-7 has become a novel tool for cancer gene therapy and is currently undergoing phase II clinical trials to determine its clinical efficacy in patients. The present review examines the biological properties of mda-7 and the signaling pathways that contribute to its unique cancer-specific apoptosis-inducing properties.
Sarkar
Devanand
D
Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Su
Zao-zhong
ZZ
Lebedeva
Irina V
IV
Sauane
Moira
M
Gopalkrishnan
Rahul V
RV
Dent
Paul
P
Fisher
Paul B
PB
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000737:chemistry / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D008322:Mammals / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012449:Safety; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000473:pathology; D000099180:Interleukin-24
D020533:Angiogenesis Inhibitors; D007378:Interleukins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D000099180:Interleukin-24