Involvement of VILIP-1 (visinin-like protein) and opposite roles of cyclic AMP and GMP signaling in in vitro cell migration of murine skin squamous cell carcinoma.
Involvement of VILIP-1 (visinin-like protein) and opposite roles of cyclic AMP and GMP signaling in in vitro cell migration of murine skin squamous cell carcinoma.
复制标题
DOI：
10.1002/mc.20707
复制
发表时间：
2011-05
影响因子：
4.6
通讯作者：
Braunewell, Karl-Heinz
中科院分区：
文献类型：
--
作者：
Schoenrath, Katharina;Pan, Wensheng;Klein-Szanto, Andres J.;Braunewell, Karl-Heinz
关键词：
VILIP-1（视见素样蛋白1）在多种人类鳞状细胞癌中下调。在小鼠皮肤SCC模型中，侵袭性肿瘤细胞中VILIP-1表达降低，伴随cAMP水平降低。VILIP-1在侵袭性SCC细胞中的过表达导致cAMP产生增强，进而导致侵袭性降低。此外，在原代神经元和神经元肿瘤系中，VILIP-1增强cGMP信号传导。在这里，我们着手确定cAMP和cGMP信号传导是否以及如何有助于VILIP-1对增强SCC模型细胞迁移的作用，从而最有可能在体内侵袭。我们发现，在攻击性，VILIP-1阴性的SCC细胞的鸟苷酸环化酶NPR-A和-B的利钠肽ANP和CNP刺激后，cGMP水平的增加更强。与ANP或8Br-cGMP孵育以增加cGMP水平进一步增强了侵袭性细胞的迁移能力，而细胞粘附不受影响。cGMP增加是由NPR-A和NPR-B的表达水平升高引起的。然而，VILIP-1的表达水平并不影响cGMP信号和鸟苷酸环化酶在SCC中的表达。相反，VILIP-1导致侵袭性SCC细胞的迁移减少，这取决于cAMP水平，如通过使用腺苷酸环化酶抑制剂2′，3 ′-二脱氧腺苷所示。cAMP效应物PKA和EPAC的参与在腺苷酸环化酶激活的下游发挥作用。VILIP-1阳性和阴性细胞在腺苷酸环化酶的mRNA表达方面没有差异，但对增强的蛋白表达和AC的膜定位的影响被证明是增强cAMP产生的基础，因此，VILIP-1减少了细胞迁移。
VILIP-1 (visinin-like protein 1) is downregulated in various human squamous cell carcinoma. In a mouse skin SCC model VILIP-1 expression is reduced in aggressive tumor cells, accompanied by reduced cAMP levels. Overexpression of VILIP-1 in aggressive SCC cells led to enhanced cAMP production, in turn causing a reduction in invasive properties. Moreover, in primary neurons and neuronal tumor lines VILIP-1 enhanced cGMP-signaling. Here, we set out to determine whether and how cAMP and cGMP-signaling contribute to the VILIP-1 effect on enhanced SCC model cell migration, and thus most likely invasiveness in vivo. We found stronger increase in cGMP levels in aggressive, VILIP-1-negative SCC cells following stimulation of guanylyl cyclases NPR-A and -B with the natriuretic peptides ANP and CNP, respectively. Incubation with ANP or 8Br-cGMP to increase cGMP levels further enhanced the migration capacity of aggressive cells, whereas cell adhesion was unaffected. Increased cGMP was caused by elevated expression levels of NPR-A and NPR-B. However, the expression level of VILIP-1 did not affect cGMP signaling and guanylyl cyclase expression in SCC. In contrast, VILIP-1 led to reduced migration of aggressive SCC cells depending on cAMP levels as shown by use of adenylyl cyclase inhibitor 2′,3′-dideoxyadenosine. Involvement of cAMP-effectors PKA and EPAC play a role downstream of adenylyl cyclase activation. VILIP-1-positive and -negative cells did not differ in mRNA expression of adenylyl cyclases, but an effect on enhanced protein expression and membrane localization of ACs was shown to underlie enhancement of cAMP production and, thus, reduction in cell migration by VILIP-1.
登录
查看更多内容
影响因子：
8
作者：
Fraser, M;Chan, SL;Tsang, BK
通讯作者：
Tsang, BK
影响因子：
4.7
作者：
Boran, Mariela Susana;Garcia, Agustina
通讯作者：
Garcia, Agustina
影响因子：
11.2
作者：
Cook, T;Wang, Z;Blumberg, D
通讯作者：
Blumberg, D
影响因子：
64.5
作者：
Guo, Dagang;Tan, Ying-cai;Huang, Xin-Yun
通讯作者：
Huang, Xin-Yun
影响因子：
4.8
作者：
Dai, Feihan F.;Zhang, Yi;Wheeler, Michael B.
通讯作者：
Wheeler, Michael B.