title: Overexpression of RhoGDI2 correlates with tumor progression and poor prognosis in colorectal carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xianzheng
authors.initials: X
authors.lastname: Li
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Zeng
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: C569658:ARHGDIB protein, human; D014408:Biomarkers, Tumor; D020730:Guanine Nucleotide Dissociation Inhibitors; D012333:RNA, Messenger; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors