Cortactin overexpression results in sustained epidermal growth factor receptor signaling by preventing ligand-induced receptor degradation in human carcinoma cells.
The chromosome 11q13 region is frequently amplified in human carcinomas and results in an increased expression of various genes including cortactin, and is also associated with an increased invasive potential. Cortactin acts as an important regulator of the actin cytoskeleton. It is therefore very tempting to speculate that cortactin is the crucial gene within the 11q13 amplicon that mediates the invasive potential of these carcinomas. Cortactin also participates in receptor-mediated endocytosis, and recent findings have shown that, during receptor internalization, cortactin overexpression inhibits the ubiquitylation-mediated degradation of the epidermal growth factor receptor, resulting in a sustained ligand-induced epidermal growth factor receptor activity.
van Rossum
Agnes G S H
AG
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. a.van.rossum@ioi.knaw.nl
Gibcus
Johan
J
van der Wal
Jacqueline
J
Schuuring
Ed
E
D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D051356:Cortactin / Q000096:biosynthesis* / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D008024:Ligands; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D015854:Up-Regulation
C495868:CTTN protein, human; D051356:Cortactin; D008024:Ligands; D066246:ErbB Receptors