Novel tumor growth inhibition mechanism by cell cycle regulator cdk2ap1 involves antiangiogenesis modulation.
Novel tumor growth inhibition mechanism by cell cycle regulator cdk2ap1 involves antiangiogenesis modulation.
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DOI：
10.1016/j.mvr.2010.06.001
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发表时间：
2010-12
影响因子：
3.1
通讯作者：
Figueiredo ML
中科院分区：
文献类型：
--
作者：
Zolochevska O;Figueiredo ML
我们评估了表达细胞周期调节蛋白 cdk2 相关蛋白 1 (cdk2ap1) 在抑制鳞状细胞癌 (SCC) 生长方面的效果。 cdk2ap1 的表达与几种 SCC 恶性细胞表型的减少相关，包括血管生成的减少。我们观察到与 cdk2ap1 的经典功能一致的基因表达的一些改变，包括细胞周期抑制基因的上调，以及属于内在和外在凋亡级联的基因表达的上调。有趣的是，我们还发现了基因表达和信号通路激活的概况，这可能表明 cdk2ap1 通过下调侵袭/转移以及通过上调 TGFβ 信号通路调节抗血管生成来发挥新的肿瘤抑制功能。阻断 TGFβ1 通路会导致 cdk2ap1 抗血管生成表型受到抑制。综合起来，这些数据支持cdk2ap1作为肿瘤抑制基因的作用，它可以通过减少侵袭性以细胞自主方式调节SCC肿瘤生长，并通过减少血管生成表型以非细胞自主方式调节SCC肿瘤生长，这些都是cdk2ap1诱导的新表型。
We evaluated the effect of expressing the cell cycle regulator protein cdk2-associating protein1 (cdk2ap1) in inhibiting growth of squamous cell carcinoma (SCC). Expression of cdk2ap1 correlated with reduction in several SCC malignant cell phenotypes, including reduced angiogenesis. We observed several alterations in gene expression consistent with classical functions of cdk2ap1, including upregulation of cell cycle inhibitory genes, and an upregulation in expression of genes belonging to both intrinsic and extrinsic apoptotic cascades. Interestingly, we also uncovered a profile of gene expression and activation of signaling pathways that may suggest new tumor-suppressive functions for cdk2ap1 through downregulation of invasion/metastasis and modulation of antiangiogenesis by upregulation of the TGFβ signaling pathway. Blocking of the TGFβ1 pathway resulted in inhibition of the cdk2ap1 antiangiogenesis phenotype. In combination, these data support the role of cdk2ap1 as a tumor suppressor gene that can regulate SCC tumor growth in a cell autonomous manner through decreases in invasiveness and a non cell-autonomous manner through decreases in angiogenesis phenotypes, and these are novel phenotypes induced by cdk2ap1.
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影响因子：
--
作者：
Jiang, Bing-Hua;Liu, Ling-Zhi
通讯作者：
Liu, Ling-Zhi
影响因子：
5.1
作者：
Koponen, JK;Kankkonen, H;Ylä-Herttuala, S
通讯作者：
Ylä-Herttuala, S
影响因子：
82.9
作者：
Gohongi, T;Fukumura, D;Jain, RK
通讯作者：
Jain, RK
影响因子：
30.8
作者：
Jenssen, TK;Lægreid, A;Hovig, E
通讯作者：
Hovig, E
影响因子：
3.8
作者：
Fenig, E;Kanfi, Y;Nordenberg, J
通讯作者：
Nordenberg, J