Bica Cecilia, Tirpe Alexandru, Nutu Andreea, Ciocan Cristina, Chira Sergiu, Gurzau Eugen S, Braicu Cornelia, Berindan-Neagoe Ioana
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400337, Romania.
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400337, Romania; Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania.
Life Sci. 2023 Apr 1;318:121499. doi: 10.1016/j.lfs.2023.121499. Epub 2023 Feb 10.
Semaphorins are regulatory molecules that are linked to the modulation of several cancer processes, such as angiogenesis, cancer cell invasiveness and metastasis, tumor growth, as well as cancer cell survival. Semaphorin (SEMA) activity depends on the cancer histotypes and their particularities. In broad terms, the effects of SEMAs result from their interaction with specific receptors/co-receptors - Plexins, Neuropilins and Integrins - and the subsequent effects upon the downstream effectors (e.g. PI3K/AKT, MAPK/ERK). The present article serves as an integrative review work, discussing the broad implications of semaphorins in cancer, focusing on cell proliferation/survival, angiogenesis, invasion, metastasis, stemness, and chemo-resistance/response whilst highlighting their heterogeneity as a family. Herein, we emphasized that semaphorins are largely implicated in cancer progression, interacting with the tumor microenvironment components. Whilst some SEMAs (e.g. SEMA3A, SEMA3B) function widely as tumor suppressors, others (e.g. SEMA3C) act as pro-tumor semaphorins. The differences observed in terms of the biological structure of SEMAs and the particularities of each cancer histotypes require that each semaphorin be viewed as a unique entity, and its roles must be researched accordingly. A more in-depth and comprehensive view of the molecular mechanisms that promote and sustain the malignant behavior of cancer cells is of utmost importance.
信号素是与多种癌症进程的调节相关的调控分子，这些进程包括血管生成、癌细胞侵袭和转移、肿瘤生长以及癌细胞存活。信号素（SEMA）的活性取决于癌症组织类型及其特殊性。广义而言，信号素的作用源于它们与特定受体/共受体（丛状蛋白、神经纤毛蛋白和整合素）的相互作用，以及随后对下游效应器（如PI3K/AKT、MAPK/ERK）的影响。本文作为一篇综合性综述文章，讨论了信号素在癌症中的广泛影响，重点关注细胞增殖/存活、血管生成、侵袭、转移、干性以及化疗耐药性/反应，同时强调它们作为一个家族的异质性。在此，我们强调信号素在很大程度上与癌症进展有关，与肿瘤微环境成分相互作用。虽然一些信号素（如SEMA3A、SEMA3B）广泛发挥肿瘤抑制作用，但其他信号素（如SEMA3C）则作为促肿瘤信号素发挥作用。信号素生物学结构方面的差异以及每种癌症组织类型的特殊性要求将每种信号素视为一个独特的实体，并相应地研究其作用。对促进和维持癌细胞恶性行为的分子机制进行更深入、全面的了解至关重要。
