Ephs and ephrins in cancer: ephrin-A1 signalling

Ephrin-A1 and its primary receptor, EphA2, are involved in numerous physiological processes and have been intensely studied for their roles in malignancy. Ephrin-Eph signalling is complex on its own and is also cell-type dependent, making elucidation of the exact role of Ephrin-A1 in neoplasia challenging. Multiple oncogenic signalling pathways, such as MAP/ERK and PI3K are affected by Ephrin-A1, and in some cases evidence suggests the promotion of a specific pathway in one cell or Cancer type and inhibition of the same pathway in another type of cell or Cancer. Ephrin-A1 also plays an integral role in angiogenesis and tumor neovascularization. Until recently, studies investigating Ephrins focused on the ligands as GPI-anchored proteins that required membrane anchoring or artificial clustering for Eph receptor activation. However, recent studies have demonstrated a functional role for soluble, monomeric Ephrin-A1. This review will focus on various forms of ephrin-A1-specific signalling in human malignancy.