Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications

Figure 1

Receptor homodimerization or heterodimerization leads to activation of downstream signaling pathways promoting cell growth, proliferation, and survival. HER2 exists in an open conformation making it the dimerization partner of choice among the family members. The PI3K/AKT axis (which is regulated by PTEN and involves other key effectors such as NFκB and mTOR) and the Raf/MAPK cascade are the two most important and most extensively studied downstream signaling pathways that are activated by the HER receptors. Ras is at the top of these cascades and acts as a self-inactivating signal transducer. A third important factor in the network is PKC, which is activated by PLC. As a result of these signaling pathways, different nuclear factors are recruited and modulate the transcription of different genes involved in cell-cycle progression, proliferation, and survival. EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor; PLC, phospholipase C; PKC, protein kinase C; PI3K, phosphatidylinositol 3-kinase; PTEN, phosphatase and tensin homolog; NFκB, nuclear factor κB; mTOR, mammalian target of rapamycin; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase.