我们前期的研究首次发现，黑色素瘤细胞中CAML是CD147的相互作用蛋白， CD147通过结合CAML能上调胞浆Ca2+的浓度和MMP-9的表达，预实验用转录因子芯片发现敲降CD147能降低NFAT1的活性。因此，我们假设 "CD147通过与CAML相互作用，增加胞质内Ca2+浓度，激活CaN-NFAT1，诱导MMPs的表达，促进黑色素瘤的侵袭转移"。为此，本项目拟分析CAML在CD147上调胞质内Ca2+浓度以及Ca2+在CD147活化CaN-NFAT1中的作用；分析NFAT1在CD147诱导MMPs表达中的作用；分析CD147、CAML、CaN、NFAT1和MMPs在黑色素瘤临床样本中的表达及临床意义。本项目研究不仅将助于揭示CD147通过与CAML相互作用介导Ca2+/NFAT1/MMPs信号通路在黑色素瘤侵袭转移中的作用及分子机制，而且能为黑色素瘤的侵袭转移预警和靶向治疗提供靶标。

Our previous experiments found that calcium-modulating cyclophilin ligand（CAML）interacted with CD147 in the endoplasmic reticulum（ER）of human malignant melanoma cells using the yeast two-hybrid system. And CD147-CAML complex can increase the intracellular Ca2+ levels by promoting Ca2+ efflux from ER to cytoplasm, then activate the related signals and effectors. And then the upregulation of MMP9 can be induced. At the same time, the activity of NFAT1, a Ca2+-dependent transcript factor, was downregulated by knockdown of CD147 expression. And knockdown of NFAT1 by siRNA can also decrease the expression of MMP9. Therefore, a series of expriments will be conducted to identify the relationships between CD147, CAML and plasma membrane Ca2+ channels, and then elucidate the mechanisms of CD147 in upregulating the cytoplasmic Ca2+ concentration. Subsequently, the activities of NFAT1 under different conditions will be analyzed to identify the way of CD147 in activating the NFAT1. Later, The roles of NFAT1 in maintaining characteristics of melanoma cells and its relationship with the CD147-mediated MMP9 expression will be studied by Chip and Luciferase gene reporter system in control melanoma cells and NFAT1 knockdown cells. Finally, the possibility of together CD147 with NFAT1 and CAML as markers for early diagnosis and prognosis of melanoma will be studied by statistical analysis of clinical documents and IHC staining results. The expected results not only are helpful to elucidate the roles and molecular mechanisms of CD147/Ca2+/NFAT1 pathway in the metastasis of malignant melanoma, but also can provide candidate molecular targets for targeted therapy of human malignant melanoma. It has important theoretical significance and practical application value.