Università Cattolica del Sacro Cuore, Rome, Italy.
Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China.
Theranostics. 2021 Jan 15;11(7):3262-3277. doi: 10.7150/thno.54023. eCollection 2021.
Semaphorins are a large family of developmental regulatory signals, characterized by aberrant expression in human cancers. These molecules crucially control cell-cell communication, cell migration, invasion and metastasis, tumor angiogenesis, inflammatory and anti-cancer immune responses. Semaphorins comprise secreted and cell surface-exposed molecules and their receptors are mainly found in the Plexin and Neuropilin families, which are further implicated in a signaling network controlling the tumor microenvironment. Accumulating evidence indicates that semaphorins may be considered as novel clinical biomarkers for cancer, especially for the prediction of patient survival and responsiveness to therapy. Moreover, preclinical experimental studies have demonstrated that targeting semaphorin signaling can interfere with tumor growth and/or metastatic dissemination, suggesting their relevance as novel therapeutic targets in cancer; this has also prompted the development of semaphorin-interfering molecules for application in the clinic. Here we will survey, in diverse human cancers, the current knowledge about the relevance of semaphorin family members, and conceptualize potential lines of future research development in this field.
信号蛋白是一类重要的发育调控信号分子家族，其在人类癌症中呈现异常表达。这些分子在细胞-细胞通讯、细胞迁移、浸润和转移、肿瘤血管生成、炎症和抗肿瘤免疫反应中起着关键作用。信号蛋白包括分泌型和细胞表面暴露型分子，其受体主要存在于 Plexin 和 Neuropilin 家族中，这些家族进一步涉及控制肿瘤微环境的信号网络。越来越多的证据表明，信号蛋白可被视为癌症的新型临床生物标志物，尤其是用于预测患者的生存和对治疗的反应性。此外，临床前实验研究表明，靶向信号蛋白信号可以干扰肿瘤生长和/或转移扩散，提示其作为癌症治疗新靶点的相关性；这也促使开发了信号蛋白干扰分子，以应用于临床。在这里，我们将在各种人类癌症中调查信号蛋白家族成员的相关性的现有知识，并提出该领域未来研究发展的潜在思路。
