Cross-talk between IGF-I and TGF-beta signaling pathways.
Insulin-like growth factor-I (IGF-I) has gained broad recognition as an important survival factor for epithelial cells in numerous tissues. The IGF-I receptor signaling pathway is deregulated in the majority of carcinomas, and such deregulation has also been reported to be tightly associated with enhanced tumor progression and metastasis. One of the key proteins that transduces IGF-I signals and is phospho-activated downstream of the IGF-I receptor, is the non-receptor serine/threonine kinase proto-oncogene protein kinase B (PKB, also known as Akt). This kinase serves as a major molecular node to control the function of many cell survival and death proteins through phosphorylation-mediated protein modification. The end result of the activation of Akt is enhanced cell survival and proliferation, pre-requisites for malignant transformation. Recent studies show that IGF-I signals cross-talk at multiple levels with various components of the TGF-beta signaling pathway, which depending on context may function either as tumor suppressor or as tumor promoter. Thus, a better understanding of how the IGF-I and TGF-beta signaling pathways are mutually interconnected is likely to unveil novel targets for the therapeutic intervention of many cancers.
Danielpour
David
D
The Case Comprehensive Cancer Center Research Laboratories, Department of Pharmacology, Case Western Reserve University, Wolstein Research Building, 2103 Cornell Road, Cleveland, OH 44106, USA. dxd49@po.cwru.edu
Song
Kyung
K
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D017526:Receptor, IGF Type 1 / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1