Growth Factor Signaling

Growth factor signaling is a complex network of communication between the cells of an organism that plays a crucial role in regulating various biological processes, including cell growth, proliferation, differentiation and survival. Growth factor signaling allows cells to receive instructions and respond accordingly to maintain tissue homeostasis and coordinate development and repair processes.

Growth factors, also known as cytokines, are small proteins or hormones secreted by cells, such as immune cells or cells in developing tissues. They influence cell behavior by binding to specific receptors on the target cell’s surface and setting off multiple signal transduction pathways that ultimately lead to changes in gene expression and cellular behavior. (1)

Growth factor receptors are membrane-bound enzyme-linked receptors that contain three domains: an extracellular domain responsible for binding of the growth factor or ligand, a transmembrane domain and a cytoplasmic domain that typically acts as an enzyme or complexes with another protein that acts as an enzyme. The majority of growth factor receptors are receptor tyrosine kinases.

Growth factor binding leads to phosphorylation of tyrosine residues on a number of intracellular signaling molecules and these molecules transmit the signal to the inside of the cell. (2)The effects of growth factor signaling are diverse and depend on the specific growth factor, receptor and target cells involved. Growth factor signaling is essential during embryonic development for the formation of organs and tissues (3), as well as for wound healing and tissue repair throughout life (4). It is also involved in maintaining tissue homeostasis, controlling cell proliferation and orchestrating immune responses.

Growth factors can be classified into many different families on the basis of their target cells, functions, structures and molecular evolution. For example, some common growth factor families that are involved in wound healing include the epidermal growth factor (EGF) family, the transforming growth factor beta (TGF-beta) family, the fibroblast growth factor (FGF) family and the vascular endothelial growth factor (VEGF) family. (4)

Growth factor signaling is tightly regulated to ensure proper cellular responses and prevent uncontrolled growth. The duration and intensity of signaling are regulated by various mechanisms, including the production of inhibitors or feedback loops that can dampen or terminate the signaling cascade. (4)

Dysregulation of growth factor signaling can have profound effects on human health. For example, excessive or prolonged growth factor signaling can contribute to cancer development by promoting uncontrolled cell growth and survival. On the other hand, insufficient growth factor signaling can lead to impaired tissue regeneration and developmental abnormalities. (5)

Understanding growth factor signaling pathways has important implications for medical research and therapeutics. Researchers are studying these pathways to develop targeted therapies for diseases like cancer, where blocking specific growth factor receptors or downstream signaling components can help inhibit tumor growth. For example, agents blocking the epidermal growth factor receptor (EGFR) have shown significant benefits in treating various solid tumors including colorectal, head and neck cancer, non-small cell lung cancer (NSCLC) and pancreatic cancer. (6)

References:

1. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Signaling through Enzyme-Linked Cell-Surface Receptors. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26822/
2. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117-1134. doi:10.1016/j.cell.2010.06.011
3. Dorey K, Amaya E. FGF signalling: diverse roles during early vertebrate embryogenesis. Development. 2010 Nov;137(22):3731-42. doi: 10.1242/dev.037689. 
4. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008 Sep-Oct;16(5):585-601. doi: 10.1111/j.1524-475X.2008.00410.x.
5. Iwata T, Hevner RF. Fibroblast growth factor signaling in development of the cerebral cortex. Dev Growth Differ. 2009 Apr;51(3):299-323. doi: 10.1111/j.1440-169X.2009.01104.x.
6. Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, Batra SK. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012 Jan;16(1):15-31. doi: 10.1517/14728222.2011.648617.