Overexpression of RhoGDI2 Correlates with Tumor Progression and Poor Prognosis in Colorectal Carcinoma

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• 作者：Xianzheng Li BSc (1) (2)
  Jianmei Wang BSc (1) (2)
  Xiaojing Zhang MSc (1) (2)
  Yuanfeng Zeng PhD (1) (2)
  Li Liang PhD (1) (2)
  Yanqing Ding MD (1) (2)
  
• 刊名：Annals of Surgical Oncology
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：19
• 期：1
• 页码：145-153
• 全文大小：1018KB
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• 作者单位：Xianzheng Li BSc (1) (2)
  Jianmei Wang BSc (1) (2)
  Xiaojing Zhang MSc (1) (2)
  Yuanfeng Zeng PhD (1) (2)
  Li Liang PhD (1) (2)
  Yanqing Ding MD (1) (2)
  
  1. Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China
  2. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, People’s Republic of China
  

文摘

Background 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. Methods 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. Results 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. Conclusions 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