According to recent evidence, some groups of semaphorins (SEMAs) have been associated with cancer progression. These proteins are able to modulate the cellular signaling of particular receptor tyrosine kinases (RTKs) via the stimulation of SEMA-specific coreceptors, namely plexins (plexin-A, -B, -C, -D) and neuropilins (Np1, Np2), which share common domains with RTKs, leading to the coactivation of the latter receptors. MET, ERBB2, VEGFR2, PFGFR, and EGFR, among others, represent acknowledged targets of semaphorins that are often associated with tumor progression or poor prognosis. In particular, higher expression of SEMA6 family proteins in cancer cells and stromal cells of the cancer niche is often associated with enhanced tumor angiogenesis, metastasis, and resistance to anticancer therapy. Notably, high SEMA6 expression in malignant tumor cells such as melanoma, pleural mesothelioma, gastric cancer, lung adenocarcinoma, and glioblastoma may serve as a prognostic biomarker of tumor progression. To date, very few studies have focused on the mechanisms of transmembrane SEMA6-driven tumor progression and its underlying interplay with RTKs within the tumor microenvironment. This review presents the growing evidence in the literature on the complex and shaping role of SEMA6 family proteins in cancer responsiveness to environmental stimuli.
最新研究证据表明，某些信号素家族蛋白与癌症进展密切相关。这类蛋白质能够通过激活其特异性共受体——包括与受体酪氨酸激酶具有共同结构域的丛状蛋白（plexin-A、-B、-C、-D型）及神经纤毛蛋白（Np1、Np2），进而调控特定受体酪氨酸激酶的细胞信号传导，最终导致这些受体的共激活。MET、ERBB2、VEGFR2、PFGFR及EGFR等已被确认为信号素的作用靶点，这些靶点常与肿瘤进展或不良预后相关。值得注意的是，SEMA6家族蛋白在癌细胞及肿瘤微环境基质细胞中的高表达，常伴随肿瘤血管生成增强、转移能力提升及抗癌治疗耐受性增加。特别是在黑色素瘤、胸膜间皮瘤、胃癌、肺腺癌和胶质母细胞瘤等恶性肿瘤细胞中，SEMA6的高表达可作为肿瘤进展的预后生物标志物。迄今为止，关于跨膜型SEMA6驱动肿瘤进展的机制及其在肿瘤微环境中与受体酪氨酸激酶的相互作用研究尚不充分。本综述系统阐述了SEMA6家族蛋白在肿瘤应答环境刺激过程中所扮演的复杂调控角色，相关文献证据正日益丰富。
肿瘤(癌症)患者之家