TRANSFORMING GROWTH FACTOR ALPHA
Transforming Growth Factor alpha (TGFα) is a 6 kDa polypeptide mitogen. Its precursor protein is a 160 amino acid integral membrane glycoprotein that is cleaved by a protease to produce the 50 amino acid mature TGFα. TGFα is produced by keratinocytes, macrophages, hepatocytes, and platelets; its synthesis is stimulated by viral infection. In mammary tissue, synthesis is stimulated by estrogen. Abundant TGFa expression is seen in transformed cells and tumors. It is expressed in modest amounts in nontransformed cells during development of mammalian embryos. TGFα is a ligand for EGFR and activates the EGFR signaling pathway promoting tumor progression by triggering downstream signaling molecules like AKT and MAPK. Studies have shown that activation of TGFα-EGFR signaling in primary colon tumors contributes to the spread of tumor cells to the lymph nodes and liver. It has also been shown that secretion of TGFα by NSCLC cells activates EGFR in tumor and tumor associated endothelial cells and EGFR signaling pathways in both tumor cells and tumor associated endothelial cells.