Giannopoulos Konstantinos, Karikis Ioannis, Byrd Chad, Sanidas Georgios, Wolff Nora, Triantafyllou Maria, Simonti Gabriele, Vidva Robinson, Koutroulis Ioannis, Theocharis Stamatios, Kratimenos Panagiotis
National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, United States.
Front Immunol. 2025 Apr 22;16:1539567. doi: 10.3389/fimmu.2025.1539567. eCollection 2025.
Eph/ephrin signaling, a complex network of cell-cell interactions, plays a pivotal role in regulating various biological processes, including cell migration, proliferation, and adhesion. Dysregulation of this signaling pathway has been implicated in various types of cancer. In skin cancers such as squamous cell carcinoma, basal cell carcinoma, and malignant melanoma, Eph/ephrin signaling promotes tumor invasion and metastasis. Aberrant expression of Eph receptors and ephrin ligands can lead to increased cell motility, reduced cell adhesion, and enhanced angiogenesis. Furthermore, Eph/ephrin signaling can significantly impact the tumor microenvironment by modulating the infiltration and activation of immune cells, particularly T cells. Dysregulated Eph/ephrin expression can impair immune surveillance mechanisms, leading to immune evasion and tumor progression. For instance, certain ephrin ligands can inhibit T-cell activation and promote immunosuppressive conditions within the tumor microenvironment. Targeting Eph/ephrin signaling offers a promising therapeutic approach to combating skin cancer metastasis. By disrupting these signaling pathways, tumor cell invasion, angiogenesis, and immune evasion can be inhibited. This could lead to improved therapeutic outcomes for patients with skin cancer.
Eph/ephrin信号传导是一个复杂的细胞间相互作用网络，在调节各种生物学过程中发挥关键作用，包括细胞迁移、增殖和黏附。该信号通路的失调与多种类型的癌症有关。在皮肤癌如鳞状细胞癌、基底细胞癌和恶性黑色素瘤中，Eph/ephrin信号传导促进肿瘤侵袭和转移。Eph受体和ephrin配体的异常表达可导致细胞运动性增加、细胞黏附减少和血管生成增强。此外，Eph/ephrin信号传导可通过调节免疫细胞特别是T细胞的浸润和激活，显著影响肿瘤微环境。Eph/ephrin表达失调可损害免疫监视机制，导致免疫逃逸和肿瘤进展。例如，某些ephrin配体可抑制T细胞激活并促进肿瘤微环境中的免疫抑制状态。靶向Eph/ephrin信号传导为对抗皮肤癌转移提供了一种有前景的治疗方法。通过破坏这些信号通路，可抑制肿瘤细胞侵袭、血管生成和免疫逃逸。这可能会改善皮肤癌患者的治疗效果。
