A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion
A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion
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DOI：
10.1074/jbc.m604376200
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发表时间：
2006-09-08
影响因子：
4.8
通讯作者：
Casey, Patrick J.
中科院分区：
文献类型：
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作者：
Kelly, Patrick;Stemmle, Laura N.;Casey, Patrick J.
许多研究表明异源三聚体G蛋白G（12）家族成员（G α（12）和G α（13））在肿瘤发生和肿瘤细胞生长中的作用。然而，很少有研究在实际的人类癌症中检测G（12）信号。在这项研究中，我们研究了G（12）信号在前列腺癌中的作用。我们发现G（12）蛋白的表达在前列腺癌中显著升高。有趣的是，在PC 3和DU 145前列腺癌细胞系中G α（12）或G α（13）的活化形式的表达并不促进癌细胞生长。相反，这些细胞系中G alpha（12）或G alpha（13）激活形式的表达通过G蛋白RhoA家族的激活诱导细胞侵袭。此外，在PC 3和DU 145细胞系中，通过表达p115-Rho特异性鸟嘌呤核苷酸交换因子（p115-RGS）的RGS结构域来抑制G（12）信号传导并没有减少癌细胞的生长。然而，在这些细胞系中，用p115-RGS抑制G（12）信号传导阻断了凝血酶和血栓烷A2刺激的细胞侵袭。这些观察鉴定了G（12）家族蛋白作为前列腺癌侵袭的重要调节因子，并表明这些蛋白可能被靶向以限制侵袭和转移诱导的前列腺癌患者死亡率。
Many studies have suggested a role for the members of the G(12) family of heterotrimeric G proteins (G alpha(12) and G alpha(13)) in oncogenesis and tumor cell growth. However, few studies have examined G(12) signaling in actual human cancers. In this study, we examined the role of G(12) signaling in prostate cancer. We found that expression of the G(12) proteins is significantly elevated in prostate cancer. Interestingly, expression of the activated forms of G alpha(12) or G alpha(13) in the PC3 and DU145 prostate cancer cell lines did not promote cancer cell growth. Instead, expression of the activated forms of G alpha(12) or G alpha(13) in these cell lines induced cell invasion through the activation of the RhoA family of G proteins. Furthermore, inhibition of G(12) signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) in the PC3 and DU145 cell lines did not reduce cancer cell growth. However, inhibition of G(12) signaling with p115-RGS in these cell lines blocked thrombin-and thromboxane A2-stimulated cell invasion. These observations identify the G(12) family proteins as important regulators of prostate cancer invasion and suggest that these proteins may be targeted to limit invasion- and metastasis-induced prostate cancer patient mortality.