Dlamini Zodwa, Mathabe Kgomotso, Padayachy Llewellyn, Marima Rahaba, Evangelou George, Syrigos Konstantinos N, Bianchi Arianna, Lolas Georgios, Hull Rodney
SAMRC Precision Prevention and Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield 0028, South Africa.
Department of Urology, University of Pretoria, Pretoria 0084, South Africa.
Cancers (Basel). 2021 Apr 29;13(9):2138. doi: 10.3390/cancers13092138.
During development, as tissues expand and grow, they require circulatory, lymphatic, and nervous system expansion for proper function and support. Similarly, as tumors arise and develop, they also require the expansion of these systems to support them. While the contribution of blood and lymphatic systems to the development and progression of cancer is well known and is targeted with anticancer drugs, the contribution of the nervous system is less well studied and understood. Recent studies have shown that the interaction between neurons and a tumor are bilateral and promote metastasis on one hand, and the formation of new nerve structures (neoneurogenesis) on the other. Substances such as neurotransmitters and neurotrophins being the main actors in such interplay, it seems reasonable to expect that alternative splicing and the different populations of protein isoforms can affect tumor-derived neurogenesis. Here, we report the different, documented ways in which neurons contribute to the development and progression of cancer and investigate what is currently known regarding cancer-neuronal interaction in several specific cancer types. Furthermore, we discuss the incidence of alternative splicing that have been identified as playing a role in tumor-induced neoneurogenesis, cancer development and progression. Several examples of changes in alternative splicing that give rise to different isoforms in nerve tissue that support cancer progression, growth and development have also been investigated. Finally, we discuss the potential of our knowledge in alternative splicing to improve tumor diagnosis and treatment.
在发育过程中，随着组织的扩张和生长，它们需要循环系统、淋巴系统和神经系统的扩张以实现正常功能并获得支持。同样，随着肿瘤的发生和发展，它们也需要这些系统的扩张来支持自身。虽然血液和淋巴系统对癌症发生和进展的作用已广为人知且成为抗癌药物的靶点，但神经系统的作用却研究较少且了解不足。最近的研究表明，神经元与肿瘤之间的相互作用是双向的，一方面促进转移，另一方面促进新神经结构（神经新生）的形成。神经递质和神经营养因子等物质是这种相互作用的主要参与者，因此可以合理推测可变剪接和不同的蛋白质异构体群体可能会影响肿瘤衍生的神经生成。在此，我们报告神经元促进癌症发生和进展的不同且有文献记载的方式，并研究目前已知的几种特定癌症类型中癌症与神经元相互作用的情况。此外，我们讨论已被确定在肿瘤诱导的神经新生、癌症发生和进展中起作用的可变剪接的发生率。还研究了可变剪接变化的几个例子，这些变化在支持癌症进展、生长和发育的神经组织中产生不同的异构体。最后，我们讨论利用我们在可变剪接方面的知识改善肿瘤诊断和治疗的潜力。
