Robert Stempel College of Public Health and Social Work, Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, HLS-594, Miami, FL 33199, USA.
Life Sci. 2010 Nov 20;87(19-22):587-95. doi: 10.1016/j.lfs.2010.09.013. Epub 2010 Sep 25.
Ca(2+) functions as an important signaling messenger right from beginning of life to the final moments of the end of life. Ca(2+) is needed at several steps of the cell cycle such as early G(1), at the G(1)/S, and G(2)/M transitions. The Ca(2+) signals in the form of time-dependent changes in intracellular Ca(2+) concentrations, Ca(2+), are presented as brief spikes organized into regenerative Ca(2+) waves. Ca(2+)-mediated signaling pathways have also been shown to play important roles in carcinogenesis such as transformation of normal cells to cancerous cells, tumor formation and growth, invasion, angiogenesis and metastasis. Since the global Ca(2+) oscillations arise from Ca(2+) waves initiated locally, it results in stochastic oscillations because although each cell has many IP(3)Rs and Ca(2+) ions, the law of large numbers does not apply to the initiating event which is restricted to very few IP(3)Rs due to steep Ca(2+) concentration gradients. The specific Ca(2+) signaling information is likely to be encoded in a calcium code as the amplitude, duration, frequency, waveform or timing of Ca(2+) oscillations and decoded again at a later stage. Since Ca(2+) channels or pumps involved in regulating Ca(2+) signaling pathways show altered expression in cancer, one can target these Ca(2+) channels and pumps as therapeutic options to decrease proliferation of cancer cells and to promote their apoptosis. These studies can provide novel insights into alterations in Ca(2+) wave patterns in carcinogenesis and lead to the development of newer technologies based on Ca(2+) waves for the diagnosis and therapy of cancer.
钙离子在生命的开始到生命结束的最后一刻都起着重要的信号信使作用。钙离子在细胞周期的几个步骤中都是必需的，如早期 G1 期、G1/S 和 G2/M 期过渡。钙离子信号以细胞内钙离子浓度[Ca2+]i 的时变形式呈现，表现为短暂的尖峰，组织成再生钙波。钙介导的信号通路也被证明在致癌作用中发挥重要作用，如正常细胞向癌细胞的转化、肿瘤的形成和生长、侵袭、血管生成和转移。由于全局 Ca2+ 振荡源于局部起始的 Ca2+ 波，因此会导致随机振荡，因为尽管每个细胞都有许多 IP3R 和 Ca2+ 离子，但大数定律不适用于起始事件，起始事件由于 Ca2+ 浓度梯度陡峭而仅限于极少数的 IP3R。特定的 Ca2+ 信号信息可能作为钙码进行编码，如 Ca2+ 振荡的幅度、持续时间、频率、波形或时间，然后在稍后阶段再次解码。由于参与调节 Ca2+ 信号通路的 Ca2+ 通道或泵在癌症中表现出改变的表达，因此可以将这些 Ca2+ 通道和泵作为治疗选择，以减少癌细胞的增殖并促进其凋亡。这些研究可以为致癌作用中 Ca2+ 波模式的改变提供新的见解，并导致基于 Ca2+ 波的新技术的发展，用于癌症的诊断和治疗。
