CRYAB Inhibits Migration And Invasion Of Bladder Cancer Cells Through The PI3K/AKT And ERK Pathways

B ackgroundBladder cancer(BC)is a common malignancy characterized by a high recurrence rate and the development of drug resistance.Frequent mutations and gene expression alterations in the P?3K-AKT and MAPK-ERK pathways lead to deregulated cell growth and the acquisition of invasive properties,which facilitates tumor progression and confers resistance to chemotherapy.Therefore,identification of the underlying mechanisms that trigger the activation of these signaling pathways and control the invasive phenotype of tumor cells is of urgent need?MethodsWe utilized publicly available gene expression databases(GEO and TCGA)and bioinformatics analysis to identify key gene expression changes in human BC.The key gene expression was detected using BC tissue microarrays.Cell proliferation,apoptosis,migration,invasion and related signaling pathways were analyzed flowing transfection with key gene overexpression plasmids.ResultsThe analysis revealed that inhibited expression of the alpha-crystallin B-chain(CRYAB)was a common feature in all analyzed datasets.The decrease in CRYAB expression was further confirmed at the protein level using BC tissue microarrays.Overexpression of CRYAB in T24 and J82 BC cell lines resulted in significant inhibition of tumor cell migration and invasion,which was associated with a decrease in P?3K,AKT and ERK activation?Moreover,CRYAB overexpression increased the expression of E-Cadherin?while reducing the expression of N-Cadherin,which indicated suppression of the epithelial-mesenchymal transition(EMT).ConclusionsOverall,the results of our study suggested that CRYAB may function as a tumor-suppressive factor in BC.