Bortner Carl D, Cidlowski John A
The Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Department of Health and Human Services, National Institutes of Health, , Research Triangle Park, NC 27709, USA.
Philos Trans R Soc Lond B Biol Sci. 2014 Feb 3;369(1638):20130104. doi: 10.1098/rstb.2013.0104. Print 2014 Mar 19.
Humans maintain a constant cell number throughout their lifespan. This equilibrium of cell number is accomplished when cell proliferation and cell death are kept balanced, achieving a steady-state cell number. Abnormalities in cell growth or cell death can lead to an overabundance of cells known as neoplasm or tumours. While the perception of cancer is often that of an uncontrollable rate of cell growth or increased proliferation, a decrease in cell death can also lead to tumour formation. Most cells when detached from their normal tissue die. However, cancer cells evade cell death, tipping the balance to an overabundance of cell number. Therefore, overcoming this resistance to cell death is a decisive factor in the treatment of cancer. Ion channels play a critical role in cancer in regards to cell proliferation, malignant angiogenesis, migration and metastasis. Additionally, ion channels are also known to be critical components of apoptosis. In this review, we discuss the modes of cell death focusing on the ability of cancer cells to evade apoptosis. Specifically, we focus on the role ion channels play in controlling and regulating life/death decisions and how they can be used to overcome resistance to apoptosis in the treatment of cancer.
人类在其整个生命周期中维持着恒定的细胞数量。当细胞增殖和细胞死亡保持平衡,实现细胞数量的稳态时,细胞数量的这种平衡就得以达成。细胞生长或细胞死亡的异常会导致细胞过度增殖,形成肿瘤。虽然人们通常认为癌症是细胞生长失控或增殖增加,但细胞死亡减少也会导致肿瘤形成。大多数细胞脱离其正常组织后会死亡。然而,癌细胞能逃避细胞死亡,使平衡向细胞数量过多倾斜。因此,克服这种对细胞死亡的抗性是癌症治疗的决定性因素。离子通道在癌症的细胞增殖、恶性血管生成、迁移和转移方面起着关键作用。此外,离子通道也是细胞凋亡的关键组成部分。在本综述中,我们将围绕癌细胞逃避细胞凋亡的能力来讨论细胞死亡的模式。具体而言,我们将重点关注离子通道在控制和调节生死抉择中所起的作用,以及它们如何用于克服癌症治疗中对细胞凋亡的抗性。