内源性CaN蛋白抑制剂RCAN1在肿瘤中的作用

The effect of RCAN1 on cancer

研究表明CaN通过调节底物蛋白NFAT激活多条细胞内信号转导通路、参与多种病理生理过程。近些年有研究报道CaN-NFAT通路也参与了肿瘤的增殖、侵袭与转移。发现CaN与肺癌嗜骨转移相关。由于外源性抑制剂对各器官组织无选择性及全身应用的毒性,限制了其应用;RCANs是一类具有高效专一低毒特点的内源CaN抑制剂,基于RCANs参与CaN/NFAT通路对CaN抑制的基础之上研究了RCAN1在神经疾病、肌萎缩、血管、免疫抑制及肿瘤中的作用。本文就CaN、NFAT、RCAN1分子结构、相互作用机制及RCAN1-CaN-NFAT通路在肿瘤中的相关研究做一综述,为寻找新的肿瘤治疗方法及药物开辟新的途径。

Many evidences indicate that Ca2＋/CaN/NFAT signaling pathway plays varied important physiological roles in the cells outside of the immune system.A novel role of calcineurin（CaN） has been reported regarding its oncogenic potential.Our study testified that calcineurin is a master molecules closely related to osteotropism metastasis of SCLC and a candidate tumor promotor gene for developing bone metastases.Pharmacological inhibition of calcineurin,by the immunosuppressive drugs cyclosporin A and FK506,affects a wide variety of diseases.But they have serious side effects,such as nephrotoxicity neurotoxicity and teratogenicity.RCAN1 is endogenous calcineurin inhibitor and has been shown to function through direct binding and inhibition of the serine threonine protein phosphatase Calcineurin.It has now been implicated in several pathological conditions including Alzheimer＇s disease,Down syndrome and cardiac hypertrophy.Some studies show that RCNA1 also play a role in cancer.We will summary the molecular structure and interaction between calcineurin RCAN1 and NFAT and also predict their foreground in translational medicine.