ABSTRACT
Triple functional domain protein (Trio) is an evolutionarily conserved protein with guanine nucleotide exchange factors that regulate different physiological processes in some types of cancer. However, the expression and function of Trio in cervical cancer are still unknown. The purpose of this study was to detect the expression of Trio in cervical cancer tissues and to evaluate its clinical value. Furthermore, the effects of the Trio on the migration and invasion of cervical cancer cells and its mechanism were investigated in vitro. The results of the present study revealed that Trio expression levels were significantly higher in most of the clinical cervical cancer samples than in adjacent tissues. The clinicopathological significance of Trio expression was also analyzed, and the results revealed that high expression levels in cervical cancer were correlated with lymph node metastasis (P=0.005). The CRISPR/Cas9 system was used to knockdown the endogenous Trio. The inhibition of Trio significantly decreased the migration and invasion abilities of cervical cancer cells. Meanwhile, levels of RhoA/ROCK signaling factors (RhoA, Rock, and p-LIMK), which contributed to cell migration and invasion, were decreased along with the inhibition of Trio. Therefore, Trio may regulate the migration and invasion of cervical cancer through the RhoA/ROCK signaling pathway.
Subject(s)
Gene Knockdown Techniques/methods , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Uterine Cervical Neoplasms/genetics , CRISPR-Cas Systems , Cell Line, Tumor , Cell Movement , Female , Gene Expression Regulation, Neoplastic , HeLa Cells , Humans , Lymphatic Metastasis , Neoplasm Invasiveness , Signal Transduction , Uterine Cervical Neoplasms/metabolism , rho-Associated Kinases/genetics , rho-Associated Kinases/metabolism , rhoA GTP-Binding Protein/genetics , rhoA GTP-Binding Protein/metabolismSubject(s)
Gynecologic Surgical Procedures/methods , Pelvic Organ Prolapse/surgery , Surgical Mesh , Adult , Aged , Female , Humans , Male , Middle Aged , Sacrum/surgery , Treatment OutcomeABSTRACT
Glioblastoma, the most common type of primary malignant brain tumor, is a devastating disease associated with a median survival of approximately 12 months. Here, we have tested E804, the commercially available indirubin derivatives, against U251 and U87 glioblastoma cells. Treatment with E804 significantly inhibits the growth of human glioblastoma cells lines via induction of differentiation and apoptosis. Differentiation induction is coupled with increased expression of glial fibriliary acidic protein, a marker for mature astrocytes. Apoptosis is associated with activation of Caspase 3 and reduction of Bcl-xL and Mcl-1. Furthermore, we demonstrate that E804 reduces signal transducer and activator of transcription-3 (Stat3) signaling to a remarkable extent, suggesting that inactivation of Stat3, at least in part, mediates the effects of this indirubin derivative. Consistently, reduction of Stat3 activity promotes E804-mediated anti-tumor effects, whereas overexpression of Stat3C mutant recues cell apoptosis induced by E804. Taken together, our results indicate that E804 can effectively suppress tumor cell growth, induce tumor cell differentiation and apoptosis mediated partially by Stat3 signaling pathway, suggesting that E804 could be useful for a potential anti-glioblastoma therapeutic approach.