A Complex Role for Calcium Signaling in Colorectal Cancer Development and Progression

Clinical data suggest that many malignant cancers are associated with hypercalcemia. Hypercalcemia can facilitate the proliferation and metastasis of gastric and colon tumors, and has been considered a hallmark of end-stage disease. However, it has also been reported that dietary calcium or vitamin D supplementation could reduce the risk of many types of cancers. In particular, the intestines can absorb considerable amounts of calcium via Ca²⁺-permeable ion channels, and hypercalcemia is common in patients with colorectal cancer. Thus, this review considers the role of calcium signaling in the context of colorectal cancer and summarizes the functions of specific regulators of cellular calcium levels in the proliferation, invasion, metastasis, cell death, and drug resistance of colorectal cancer cells. The data reveal that even a slight upregulation of intracellular Ca²⁺ signaling can facilitate the onset and progression of colorectal cancer, while continuous Ca²⁺ influx and Ca²⁺ overload may cause tumor cell death. This dual function of Ca²⁺ signaling adds nuance to the debate over the hallmarks of colorectal cancer, and may even provide new directions and strategies for clinical interventions.