Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12.
Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12.
复制标题
DOI：
10.1007/s10555-012-9360-1
复制
发表时间：
2012-12
影响因子：
9.2
通讯作者：
Gelman, Irwin H.
中科院分区：
文献类型：
--
作者：
Gelman, Irwin H.
支架蛋白如SSeCKS/Gravin/AKAP 12（“AKAP 12”）被认为通过以时空方式调节关键介质来控制致癌信号传导途径。AKAP 12在许多人类癌症中的下调，通常与启动子超甲基化或其6 q24 -25.2位点的缺失相关，与恶性肿瘤和转移的进展相关。AKAP 12在癌细胞系中的强制再表达通过其支架蛋白激酶C（PKC）、F-肌动蛋白、细胞周期蛋白、Src和磷酸肌醇的能力，以及可能通过PKA、钙调蛋白、β 1，4-半乳糖基转移酶-多肽-1、β2-肾上腺素能受体和cAMP特异性3′，5 ′-环磷酸二酯酶4D的额外支架结构域，抑制致癌生长、侵袭性和细胞运动性的体外参数。此外，AKAP 12在肿瘤模型中的再表达通过抑制Src调节的VEGF介导的远端部位的新血管形成而导致转移抑制。目前的综述将描述AKAP 12如何通过其多种支架功能在肿瘤细胞和肿瘤相关微环境水平上调节细胞衰老和致癌进展的新认识。
Scaffolding proteins such as SSeCKS/Gravin/AKAP12 (“AKAP12”) are thought to control oncogenic signaling pathways by regulating key mediators in a spatiotemporal manner. The downregulation of AKAP12 in many human cancers, often associated with promoter hypermethylation, or the loss of its locus at 6q24-25.2, correlates with progression to malignancy and metastasis. The forced re-expression of AKAP12 in cancer cell lines suppresses in vitro parameters of oncogenic growth, invasiveness and cell motility through its ability to scaffold protein kinase C (PKC), F-actin, cyclins, Src and phosphoinositides, and possibly through additional scaffolding domains for PKA, calmodulin, β1,4-galactosyltransferase-polypeptide-1, β2-adrenergic receptors and cAMP-specific 3′,5′-cyclic phosphodiesterase 4D. Moreover, AKAP12 re-expression in tumor models results in metastasis suppression through the inhibition of Src-regulated, VEGF-mediated neovascularization at distal sites. The current review will describe the emerging understanding of how AKAP12 regulates cellular senescence and oncogenic progression at the level of tumor cells and tumor-associated microenvironment via its multiple scaffolding functions.
登录
查看更多内容
影响因子：
--
作者：
Gao S;Wang HY;Malbon CC
通讯作者：
Malbon CC
影响因子：
6.4
作者：
Akakura, Shin;Bouchard, Rene;Bshara, Wiam;Morrison, Carl;Gelman, Irwin H.
通讯作者：
Gelman, Irwin H.
影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
3.8
作者：
Adrien, Daigeler;Ludger, Klein-Hitpass;Michael, Chromik Ansgar;Oliver, Mueller;Joerg, Hauser;Heinz-Herbert, Homann;Hans-Ulrich, Steinau;Marcus, Lehnhardt
通讯作者：
Marcus, Lehnhardt
影响因子：
8
作者：
Cohen, SB;Waha, A;Vogt, PK
通讯作者：
Vogt, PK