Retinoid and Growth Factor Signal Transduction

Abstract Retinoids play a significant role in cell growth and differentiation and suppress cancer invasion and metastasis. Retinoids are also able to modulate cellular responses to growth factors. In this review we discuss the pathways of transduction of signals imparted to the cell by retinoids and growth factors. Three pathways of flow of information are identified, defined, and discussed. The receptors mediated pathway of information flow is briefly discussed with reference to the regulation of transcription factors by retinoic acids. Information transfer also occurs via the agency of integrin receptors. The intracellular down-stream events involve phosphorylation of substrate proteins such as the focal adhesion kinases. The cytoskeleton is involved in the flow of information that results from retinoic acid or growth factor exposure of cells. There are clear indications of disruption of the tubulin and actin cytoskeletal elements, which appears to lead to the progression of the cell cycle into the S-phase. The transduction of growth factor binding signals involves a number of intracellular nonreceptor kinases that act as signaling proteins. These contain src homology domains. These src homology domain proteins appear to be involved also in interactions with the cytoskeletal assembly. Growth factors and hormones alter levels of intracellular calcium, which controls many cellular functions. The Ca 2 + signaling pathway may also be involved in genetic responses to retinoic acid, either directly or by modulating the expression of genes that code for calcium binding proteins such as the 18A2/mts1 protein. Other genetic targets can also be identified. There is much circumstantial evidence that the expression of heat shock proteins may be regulated by retinoic acid. Heat shock proteins might conceivably play an important part in recruiting essential components to the cytoskeleton for intracellular translocation or simply in altering the cytoskeletal dynamics, which has a significant bearing on cell shape, motility and invasion, and signal transduction.