Regulator of calcineurin 1 modulates cancer cell migration in vitro.
Regulator of calcineurin 1 modulates cancer cell migration in vitro.
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DOI：
10.1007/s10585-009-9251-1
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发表时间：
2009
影响因子：
4
通讯作者：
Ringel, Matthew D.
中科院分区：
文献类型：
--
作者：
Espinosa, Allan V.;Shinohara, Motoo;Porchia, Leonardo M.;Chung, Yun Jae;McCarty, Samantha;Saji, Motoyasu;Ringel, Matthew D.
转移抑制因子和其他细胞运动调节因子在肿瘤侵袭和转移中起重要作用。我们之前发现，转移抑制因子转移蛋白激活G蛋白偶联受体54 （GPR54）可抑制细胞迁移，这与钙调神经磷酸酶1调节剂（RCAN1）的过表达有关，这是一种内源性钙调神经磷酸酶调节剂。钙调磷酸酶抑制剂也阻断了细胞的体外迁移，RCAN1蛋白水平在甲状腺癌淋巴结转移中降低。当前研究的目的是直接确定RCAN1是否在体外作为运动抑制因子起作用。几种来自不同癌症类型的具有不同运动率的癌细胞系被评估了RCAN1表达水平。使用这些系统，我们确定使用siRNA减少内源性RCAN1导致癌细胞运动增加，而外源性RCAN1的表达降低了细胞运动。在一个高迁移率的细胞系中，外源表达的RCAN1蛋白的稳定性降低，并通过蛋白酶体抑制剂处理得到恢复。最后，RCAN1的过表达与细胞粘附于IV型胶原蛋白的增加和钙调磷酸酶活性的降低有关。总之，我们已经证明外源性RCAN1的表达减少了迁移并改变了粘附；并且内源性RCAN1的缺失导致在所检测的癌细胞系中迁移的增加。这些结果与RCAN1在体外癌细胞运动中的调节作用一致。
Metastasis suppressors and other regulators of cell motility play an important role in tumor invasion and metastases. We previously identified that activation of the G protein coupled receptor 54 (GPR54) by the metastasis suppressor metastin inhibits cell migration in association with overexpression of Regulator of calcineurin 1 (RCAN1), an endogenous regulator of calcineurin. Calcineurin inhibitors also blocked cell migration in vitro and RCAN1 protein levels were reduced in nodal metastases in thyroid cancer. The purpose of the current study was to determine directly if RCAN1 functions as a motility suppressor in vitro. Several cancer cell lines derived from different cancer types with different motility rates were evaluated for RCAN1 expression levels. Using these systems we determined that reduction of endogenous RCAN1 using siRNA resulted in an increase in cancer cell motility while expression of exogenous RCAN1 reduced cell motility. In one cell line with a high migratory rate, the stability of exogenously expressed RCAN1 protein was reduced and was rescued by treatment with a proteasome inhibitor. Finally, overexpression of RCAN1 was associated with an increase in cell adhesion to collagen IV and reduced calcineurin activity. In summary, we have demonstrated that the expression of exogenous RCAN1 reduces migration and alters adhesion; and that the loss of endogenous RCAN1 leads to an increase in migration in the examined cancer cell lines. These results are consistent with a regulatory role for RCAN1 in cancer cell motility in vitro.
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影响因子：
6.6
作者：
Hoffmann, S;Maschuw, K;Zielke, A
通讯作者：
Zielke, A
影响因子：
4.8
作者：
Muir, AI;Chamberlain, L;Harrison, DC
通讯作者：
Harrison, DC
影响因子：
10.3
作者：
Nash, Kevin T.;Phadke, Pushkar A.;Welch, Danny R.
通讯作者：
Welch, Danny R.
DOI：
10.1126/science.1161621
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Podsypanina K;Du YC;Jechlinger M;Beverly LJ;Hambardzumyan D;Varmus H
通讯作者：
Varmus H
DOI：
10.1006/bbrc.2001.5470
发表时间：
2001-09-07
影响因子：
3.1
作者：
Hori, A;Honda, S;Fujino, M
通讯作者：
Fujino, M