Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, P.R. China.
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, P.R. China.
Mol Cancer Res. 2019 Nov;17(11):2145-2153. doi: 10.1158/1541-7786.MCR-19-0429. Epub 2019 Jul 31.
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 Ca-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 Ca signaling can facilitate the onset and progression of colorectal cancer, while continuous Ca influx and Ca overload may cause tumor cell death. This dual function of Ca signaling adds nuance to the debate over the hallmarks of colorectal cancer, and may even provide new directions and strategies for clinical interventions.
临床数据表明，许多恶性癌症与高钙血症有关。高钙血症可促进胃和结肠肿瘤的增殖和转移，并且被认为是终末期疾病的标志。然而，也有报道称，饮食中钙或维生素 D 的补充可能会降低多种癌症的风险。特别是，肠道可以通过钙渗透性离子通道吸收大量的钙，而高钙血症在结直肠癌患者中很常见。因此，本综述考虑了钙信号在结直肠癌中的作用，并总结了细胞内钙水平的特定调节剂在结直肠癌细胞增殖、侵袭、转移、细胞死亡和耐药性中的功能。这些数据表明，即使是细胞内 Ca 信号的轻微上调也可以促进结直肠癌的发生和发展，而持续的 Ca 内流和 Ca 过载可能导致肿瘤细胞死亡。Ca 信号的这种双重功能为结直肠癌的标志性特征的争论增添了细微差别，甚至可能为临床干预提供新的方向和策略。
