Overexpression of RhoGDI2 Correlates with Tumor Progression and Poor Prognosis in Colorectal Carcinoma
Overexpression of RhoGDI2 Correlates with Tumor Progression and Poor Prognosis in Colorectal Carcinoma
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DOI：
10.1245/s10434-011-1944-4
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发表时间：
2012-01-01
影响因子：
3.7
通讯作者：
Ding, Yanqing
中科院分区：
文献类型：
--
作者：
Li, Xianzheng;Wang, Jianmei;Ding, Yanqing
RhoGDI2已被确定为肿瘤转移的调节因子，但其在癌症中的作用仍存在争议。为探讨RhoGDI2在结直肠癌中的作用，探讨RhoGDI2在结直肠癌中可能的信号转导途径。采用实时荧光定量RT-PCR、Western印迹、RT-PCR或免疫组织化学方法检测RhoGDI2在结直肠癌细胞系、20对配对新鲜结直肠癌组织和120例临床石蜡包埋组织中的表达。Western印迹法检测RhoGDI2过表达细胞中p-PI3K、p-Akt、p-MAPK和p-MEK的激活水平。结果表明，RhoGDI2在高转移结直肠癌细胞系中的表达高于低转移结直肠癌细胞系。RhoGDI2在结直肠癌或淋巴转移癌组织中的表达高于正常粘膜(P<；0.05)。RhoGDI2的表达与肿瘤大小、分化程度和Duke‘s分期密切相关(P<；0.05)。RhoGDI2低表达患者的总生存率较高(P=0.012)，RhoGDI2仅能预测早期疾病患者的预后。在RhoGDI2过表达的细胞中观察到高水平的p-PI3K和p-Akt的激活。LY294002抑制剂可阻断PI3K/Akt通路的激活。RhoGDI2过表达促进了结直肠癌细胞的增殖、迁移和体外侵袭。RhoGDI2过表达与结直肠癌患者，尤其是早期结直肠癌患者的总体生存率较低有关。RhoGDI2至少部分通过激活PI3K/Akt通路促进细胞增殖、运动和侵袭结直肠癌。
RhoGDI2 has been identified as a regulator of tumor metastasis but its role in cancer remains controversial. The aims of this study were to analyze the function of RhoGDI2 in colorectal carcinoma (CRC), and to determine its possible signaling pathway in CRC.The expression of RhoGDI2 was detected in CRC cell lines, and 20 matched pairs of fresh CRC tissues, and 120 cases of clinical paraffin-embedded CRC tissues by real-time RT-PCR, Western blot, RT-PCR, or immunohistochemistry. The levels of activations of p-PI3K, p-Akt, p-MAPK, and p-MEK were then examined in RhoGDI2-overexpressing cells by Western blot. A series of assays were finally performed to evaluate the effect of RhoGDI2 on CRC cell behaviors in vitro.RhoGDI2 expression was higher in highly metastatic CRC cell lines than in lowly metastatic ones. RhoGDI2 expression was up-regulated in CRC or lymphatic metastatic tissues relative to normal mucosa (P < 0.05). RhoGDI2 expression was correlated strongly with tumor size, differentiation, and Duke's stage (P < 0.05). Patients with lower RhoGDI2 expression had better overall survival (P = 0.012), and RhoGDI2 could predict prognosis only in patients with early-stage disease. High levels of activations of p-PI3K and p-Akt were observed in RhoGDI2-overexpressing cells. LY294002 inhibitor could abrogate the activation of PI3K/Akt pathway in those cells. Over-expression of RhoGDI2 enhanced CRC cell proliferation, motility, and invasion in vitro.Over-expression of RhoGDI2 is associated with poor overall survival in CRC patients, especially those presenting in early-stage. RhoGDI2 contributes to cell proliferation, motility, and invasion of CRC, at least in part, by activating the PI3K/Akt pathway.