Targeting the Epidermal Growth Factor Receptor in Epithelial Ovarian Cancer: Current Knowledge and Future Challenges
Figure 2
Selected representation of canonical EGFR family signaling pathways. The EGFR family consists of 4 members: EGFR, HER2, HER3, and HER4 (indicated by numbers 1–4 in the diagram). EGFR family ligands include EGF-and EGF-like ligands, transforming growth factor (TGF)- and heregulins (HRGs, also known as neuregulins, NRGs). As indicated by the numbers in parentheses beneath the ligands, each ligand binds preferentially to a particular EGFR family member. HER2, while lacking any known ligand, is the preferred binding partner of for all EGFR family members. HER3 lacks intrinsic kinase activity due to mutation of critical amino acids in the kinase domain; therefore, it is inactive on its own or as a homodimer. Transduction of EGFR signals occurs through intracellular adaptor proteins, which transmit signals through cascades such as the RAS/RAF/MEK/mitogen-activated protein kinase (MAPK) and phosphatidylinositol -kinase (PI3K)/AKT cascades. The downstream proteins in these signaling cascades can shuttle from the cytoplasm to the nucleus, where they signal to transcription factors and their complexes such as MYC, ELK, and FOS/JUN. Signal transduction through the EGFR family to downstream pathways and cascades controls diverse cellular responses such as proliferation, differentiation, cell motility, and survival as well as tumorigenesis. Figure adapted from [13]. Abbreviations: PLC: Phospholipase C; SHP2: SRC homology phosphatase 2; GAP: GTPase activating protein; SHC: SRC homology 2 domain and collagen-containing protein; PKC: Protein kinase C; MEK: MAPK/ERK kinase; PAK: P21-activated kinase; JNKK: JNK kinase; JNK: JUN N-terminal kinase; EGR1: Early growth response protein 1; STAT: Signal transducer and activator of transcription.
