title: Knockdown of Rab5a expression decreases cancer cell motility and invasion through integrin-mediated signaling pathway.
abstract: BACKGROUND
  Rab GTPases function as modulators in intracellular transport. Rab5a, a member of the Rab subfamily of small GTPases, is an important regulator of vesicle traffic from the plasma membrane to early endosomes. Recent findings have reported that Rab5a gene was involved in the progression of cancer. In the present study, we investigated the effect of Rab5a on cervical cancer invasion and metastasis and the molecular mechanism underlying the involvement of Rab5a.
  
  
  METHODS
  Rab5a expression was assessed by immunohistochemical analysis on a cervical cancer tissue microarray. RNA interference (RNAi) was performed to knock down the endogenous expression of Rab5a gene in HeLa and SiHa cells. Cell motility was evaluated using invasion assay and wound migration assay in vitro. The expression levels of integrin-associated molecules were detected by Western blot and immunofluorescence.
  
  
  RESULTS
  We found that Rab5a was expressed at a high level in cervical cancer tissues. Silencing of Rab5a expression significantly decreased cancer cell motility and invasiveness. The down-regulation of integrin-associated focal adhesion signaling molecules was further detected in Rab5a knockdown cells. Meanwhile, active GTP-bound Rac1, Cdc42, and RhoA were also down-regulated, accompanied with the reduction in the number and size of filopodia and lamellipodia.
  
  
  CONCLUSIONS
  Taken together, these data suggest that Rab5a functions in regulating the invasion phenotype, and we propose that this regulation may be via integrin-mediated signaling pathway in cervical cancer cells.
authors.affiliation: Department of Life Science and Engineering, Harbin Institute of Technology, Harbin 150001, PR China. liyugene@hit.edu.cn
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Liu
authors.forename: Xiang-mei
authors.initials: XM
authors.lastname: Chen
authors.forename: Hong-xia
authors.initials: HX
authors.lastname: Zheng
authors.forename: Shu-liang
authors.initials: SL
authors.lastname: Shi
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016023:Integrins; D020696:rab5 GTP-Binding Proteins