Xu MengMeng, Seas Andreas, Kiyani Musa, Ji Keven S Y, Bell Hannah N
1Medical-Scientist Training Program, Duke University Medical Center, Durham, NC 27710 USA.
2Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710 USA.
Cell Biosci. 2018 Apr 3;8:25. doi: 10.1186/s13578-018-0223-5. eCollection 2018.
Although the study of calcium (Ca) is classically associated with excitable cells such as myocytes or neurons, the ubiquity of this essential element in all cellular processes has led to interest in other cell types. The importance of Ca to apoptosis, cell signaling, and immune activation is of special import in cancer.
Here we review the current understanding of Ca in each of these processes vital to the initiation, spread, and drug resistance of malignancies. We describe the involvement of Ca, and Ca related proteins in cell cycle checkpoints and Ca dependent apoptosis and discuss their roles in cellular immortalization. The role of Ca in inter-cellular communication is also discussed in relevance to tumor-stromal communication, angiogenesis, and tumor microinvasion. The role that Ca plays in immune surveillance and evasion is also addressed. Finally, we discuss the possibility of targeting Ca singling to address the most pressing topics of cancer treatment: metastatic disease and drug resistance.
This review discusses the current understanding of Ca in cancer. By addressing Ca facilitated angiogenesis, immune evasion, metastasis, and drug resistance, we anticipate future avenues for development of Ca as a nexus of therapy.
尽管钙(Ca)的研究传统上与可兴奋细胞如心肌细胞或神经元相关,但这种必需元素在所有细胞过程中的普遍性引发了对其他细胞类型的兴趣。钙对细胞凋亡、细胞信号传导和免疫激活的重要性在癌症中具有特殊意义。
在此,我们综述了目前对钙在恶性肿瘤的起始、扩散和耐药性等这些至关重要的过程中的理解。我们描述了钙以及与钙相关的蛋白质在细胞周期检查点和钙依赖性细胞凋亡中的作用,并讨论它们在细胞永生化中的作用。还讨论了钙在细胞间通讯中的作用,涉及肿瘤与基质的通讯、血管生成和肿瘤微侵袭。也阐述了钙在免疫监视和免疫逃逸中的作用。最后,我们讨论了靶向钙信号传导以解决癌症治疗最紧迫问题——转移性疾病和耐药性的可能性。
本综述讨论了目前对癌症中钙的理解。通过探讨钙促进血管生成、免疫逃逸、转移和耐药性方面的问题,我们预期未来将钙作为治疗关键环节的发展途径。