S100A4 promotes pancreatic cancer progression through a dual signaling pathway mediated by Src and focal adhesion kinase.
S100A4 promotes pancreatic cancer progression through a dual signaling pathway mediated by Src and focal adhesion kinase.
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DOI：
10.1038/srep08453
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发表时间：
2015-02-13
影响因子：
4.6
通讯作者：
Ding Q
中科院分区：
文献类型：
--
作者：
Che P;Yang Y;Han X;Hu M;Sellers JC;Londono-Joshi AI;Cai GQ;Buchsbaum DJ;Christein JD;Tang Q;Chen D;Li Q;Grizzle WE;Lu YY;Ding Q
S100 A4表达与胰腺癌患者的不良临床结局相关。在胰腺癌细胞系中检查S100 A4的丧失或获得的影响。S100 A4下调显著减少胰腺癌细胞的迁移和侵袭，抑制增殖，并诱导凋亡。S100 A4下调导致显著的细胞生长抑制和细胞凋亡，从而响应于TGF-β1，支持S100 A4在胰腺癌中的非典型作用。通过使用原位人胰腺癌异种移植小鼠模型研究S100 A4在肿瘤进展中的作用。在注射S100 A4缺陷胰腺肿瘤细胞的动物中，肿瘤质量显著降低。在体内S100 A4缺陷的胰腺肿瘤中，P27 Kip 1表达和裂解的caspase-3增加，而细胞周期蛋白E表达减少。S100 A4缺陷型肿瘤的血管内皮生长因子表达较低，提示血管生成减少。生物化学分析显示，S100 A4激活Src和粘着斑激酶（FAK）信号传导事件，并且需要抑制这两种激酶以最大限度地阻断胰腺癌细胞的致瘤潜力。这些发现支持S100 A4在胰腺癌体内进展中起重要作用，并且S100 A4通过Src-FAK介导的双重信号通路促进胰腺癌细胞的致瘤表型。
S100A4 expression is associated with poor clinical outcomes of patients with pancreatic cancer. The effects of loss or gain of S100A4 were examined in pancreatic cancer cell lines. S100A4 downregulation remarkably reduces cell migration and invasion, inhibits proliferation, and induces apoptosis in pancreatic tumor cells. S100A4 downregulation results in significant cell growth inhibition and apoptosis in response to TGF-β1, supporting a non-canonical role of S100A4 in pancreatic cancer. The role of S100A4 in tumor progression was studied by using an orthotopic human pancreatic cancer xenograft mouse model. Tumor mass is remarkably decreased in animals injected with S100A4-deficient pancreatic tumor cells. P27Kip1 expression and cleaved caspase-3 are increased, while cyclin E expression is decreased, in S100A4-deficient pancreatic tumors in vivo. S100A4-deficient tumors have lower expression of vascular endothelial growth factor, suggesting reduced angiogenesis. Biochemical assays revealed that S100A4 activates Src and focal adhesion kinase (FAK) signaling events, and inhibition of both kinases is required to maximally block the tumorigenic potential of pancreatic cancer cells. These findings support that S100A4 plays an important role in pancreatic cancer progression in vivo and S100A4 promotes tumorigenic phenotypes of pancreatic cancer cells through the Src-FAK mediated dual signaling pathway.
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影响因子：
8
作者：
Han, XS;Stewart, JE;Gladson, CL
通讯作者：
Gladson, CL
影响因子：
45.3
作者：
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通讯作者：
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影响因子：
8
作者：
Ambartsumian, N;Klingelhöfer, J;Lukanidin, E
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影响因子：
8
作者：
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通讯作者：
Gladson, CL
DOI：
10.1152/ajplung.00390.2011
发表时间：
2012-10-01
影响因子：
4.9
作者：
Cai, Guo-Qiang;Chou, Chu-Fang;Ding, Qiang
通讯作者：
Ding, Qiang