Figure 4.

Hypothetical mechanism of breast cancer cell colonization of the brain parenchyma. Hypoxic conditions, (HIF1a) can mediate the elease of neuregulin 1 from neuronal cells. Neuregulin 1 is the ligand for HER3 and on binding activates the heterodimerisation of HER3-HER2, HER3-HER4 and/or HER3-HER1, leading to downstream activation of the MAPK and AKT pathways. MAPK/AKT pathways activation is related to survival, invasion, proliferation and angiogenesis. A second mechanism of colonization may relate to the enriched expression of CD44 breast cancer cells in the brain. The brain microenvironment is rich in hyaluron, the ligand for CD44, and so upon activation a series of responses maybe triggered, including cell motility.