Knockdown of Rab5a expression decreases cancer cell motility and invasion through integrin-mediated signaling pathway

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.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.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.Cancer is a leading cause of mortality worldwide. Invasion and metastasis is the main biological characteristics of cancer cells, and the major cause of death in patients with cancer. The investigation concerning tumor cell invasion and metastasis has become the focus of intense researches. However, the molecular mechanism of the progression of cancer cell invasion and metastasis has not been fully elucidated.Small GTPases of the Ras superfamily function as molecular switches that involve in the control of a large variety intracellular processes, including proliferation and differentiation, gene expression, signal transduction, vesicle trafficking, nuclear assembly, and reorganization of cytoskeleton. Most of these small GTPases cycle between two forms: an active GTP-bound form and an inactive GDP-bound form. GTPase activating proteins (GAPs) promote the GDP-bound state of small GTPases by activating their intrinsic G