Plasma membrane calcium pumps and their emerging roles in cancer

Figure 1 A schematic representation of the possible link between plasma membrane calcium ATPase expression level, cytoplasmic calcium level and cancer relevant pathways. A representative calcium trace is shown to illustrate how the cytoplasmic calcium signal, such as the amplitude, might be affected by the level of plasma membrane calcium ATPase (PMCA) expression. High PMCA expression levels that reduce the cytoplasmic calcium signal (e.g. decreased amplitude) might enable a cancer cells to resist apoptosis. Alternatively, where PMCA expression is at low levels and the cytoplasmic calcium signal is increased (e.g. increase in amplitude) activation of prosurvival transcription and enhanced proliferation would facilitate cancer progression. In contrast, a pronounced reduction in PMCA expression, where the cytoplasmic calcium signal is significantly augmented (e.g. a significant increase in amplitude) an antitumor effect may result where the cells are sensitized to apoptosis.