Department of Neurosurgery, Brain Tumor Center of Excellence, Comprehensive Cancer Center of Wake Forest University, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Semin Cell Dev Biol. 2012 Feb;23(1):109-15. doi: 10.1016/j.semcdb.2011.10.019. Epub 2011 Oct 25.
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.
Ephrin-A1 及其主要受体 EphA2 参与了许多生理过程，并因其在恶性肿瘤中的作用而受到深入研究。Ephrin-Eph 信号本身就很复杂，而且还依赖于细胞类型，这使得阐明 Ephrin-A1 在肿瘤发生中的确切作用具有挑战性。多种致癌信号通路，如 MAP/ERK 和 PI3K，受 Ephrin-A1 影响，在某些情况下，有证据表明 Ephrin-A1 在一种细胞或癌症类型中促进特定通路，而在另一种类型的细胞或癌症中抑制相同通路。Ephrin-A1 还在血管生成和肿瘤新生血管形成中发挥重要作用。直到最近，研究 Ephrins 的研究还集中在作为 GPI 锚定蛋白的配体上，这些配体需要膜锚定或人工聚类才能激活 Eph 受体。然而，最近的研究表明可溶性单体 Ephrin-A1 具有功能作用。这篇综述将重点介绍 Ephrin-A1 在人类恶性肿瘤中的各种特定信号形式。
