Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells
Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells
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平衡的 Tiam1-Rac1 和 RhoA 驱动胰腺癌细胞的增殖和侵袭
DOI：
10.1158/1541-7786.mcr-12-0632
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发表时间：
2013-03-01
影响因子：
5.2
通讯作者：
Qin, Renyi
中科院分区：
文献类型：
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作者：
Guo, Xingjun;Wang, Min;Qin, Renyi
Tiam1 是 rac1 特异性鸟嘌呤核苷酸交换因子，Tiam1-rac1 参与许多细胞过程。 Rac1 和 RhoA 作为分子开关，在 GTP 和 GDP 结合状态之间循环，以平衡 rac1 和 RhoA 的活性。 rac1活性下调导致RhoA活性上调，从而促进胰腺癌细胞的侵袭和迁移。然而目前Tiam1-rac1和RhoA在胰腺癌中的作用尚未完全清楚。我们发现 Tiam1 在胰腺癌中表达上调，并且与有淋巴结受累或远处转移的肿瘤相比，在没有淋巴结受累或远处转移的肿瘤中显着表达。尽管 Tiam1-rac1 信号在体外和体内通过 Wnt 信号通路促进胰腺癌细胞增殖和肿瘤生长，但抑制 Tiam1-rac1 信号并不能延长体内总生存时间。这提供了证据表明胰腺癌中 rac1 和 RhoA 活性之间存在平衡。此外，只有 Tiam1-rac1 和 RhoA 的联合抑制才对体内胰腺癌的生长产生有益作用。综上所述，这些结果表明胰腺肿瘤的进展部分由 Tiam1-rac1 和 RhoA 之间的平衡控制。摩尔癌症研究中心； 11(3)； 230–9。 ©2012 AACR。
Tiam1 is a rac1-specific guanine nucleotide exchange factor, and Tiam1-rac1 is involved in a number of cellular processes. Rac1 and RhoA act as molecular switches that cycle between GTP- and GDP-bound states to balance the activities of rac1 and RhoA. The downregulation of rac1 activity leads to upregulation of RhoA activity, which promotes invasion and migration of pancreatic cancers cells. At present, however, the role of Tiam1-rac1 and RhoA in pancreatic cancers is not fully understood. We found that Tiam1 was upregulated in pancreatic cancers and was significantly expressed in tumors without lymph node involvement or distant metastasis compared with cancers where there was involvement. Although Tiam1-rac1 signaling promoted pancreatic cancer cell proliferation and tumor growth via the Wnt signaling pathway in vitro and in vivo, inhibiting Tiam1-rac1 signaling did not prolong the overall survival time in vivo. This provided evidence that there was a balance between rac1 and RhoA activities in pancreatic cancers. Furthermore, only the combined inhibition of Tiam1-rac1 and RhoA had a beneficial effect on the growth of pancreatic cancers in vivo. Taken together, these results suggest that the progression of pancreatic tumors is partially controlled by the balance between Tiam1-rac1 and RhoA. Mol Cancer Res; 11(3); 230–9. ©2012 AACR.