Abstract
Background and methodsIn addition to possess cross drug resistance characteristic, emerging evidences have shown that multiple-drug resistance (MDR) cancer cells exhibit aberrant metastatic capacity when compared to parental cells. In this study, we explored the contribution of c-Jun N-terminal kinases (JNK) signaling to the mesenchymal phenotypes and the aberrant motile capacity of MDR cells utilizing a well characterized MDR cell line KB/VCR, which is established from KB human epidermoid carcinoma cells by vincristine (VCR), and its parental cell line KB.ResultsTaking advantage of experimental strategies including pharmacological tool and gene knockdown, we showed here that interference with JNK signaling pathway by targeting JNK1/2 or c-Jun reversed the mesenchymal properties of KB/VCR cells to epithelial phenotypes and suppressed the motile capacity of KB/VCR cells, such as migration and invasion. These observations support a critical role of JNK signaling in maintaining the mesenchymal properties of KB/VCR cells. Furthermore, we observed that JNK signaling may control the expression of both snail and twist1 in KB/VCR cells, indicating that both snail and twist1 are involved in controlling the mesenchymal characteristics of KB/VCR cells by JNK signaling.ConclusionJNK signaling is required for maintaining the mesenchymal phenotype of KB/VCR cells; and JNK signaling may maintain the mesenchymal characteristics of KB/VCR cells potentially through snail and twist1.
Highlights
Background and methodsIn addition to possess cross drug resistance characteristic, emerging evidences have shown that multiple-drug resistance (MDR) cancer cells exhibit aberrant metastatic capacity when compared to parental cells
This study explored the influences of Jun N-terminal kinases (JNK) signaling on epithelial-mesenchymal transition (EMT) of MDR cells to dissect the potential mechanisms underlying the aberrant motile capacity of MDR cells using a well characterized MDR cell line KB/VCR, a subline established from a human epidermoid carcinoma cell line KB by vincristine (VCR), and its parental KB cells [15]
KB/VCR cells exhibit mesenchymal properties and aberrant motile capacity compared to the parental cells KB We employed the MDR cell line KB/VCR, a well established MDR cell line [15], to firstly explore whether the MDR cells possess mesenchymal properties
Summary
Background and methodsIn addition to possess cross drug resistance characteristic, emerging evidences have shown that multiple-drug resistance (MDR) cancer cells exhibit aberrant metastatic capacity when compared to parental cells. For metastasis from a primary tumor site, cancer cells must lose cell-cell adhesion and acquire motility to invade adjacent cell layers [6] This process shares many similarities with epithelial-mesenchymal transition (EMT), which has been proposed as one of critical mechanisms for the acquisition of metastatic capacity by epithelial cancer cells [7]. EMT, a highly conserved cellular program in many important phases of embryonic development, is a biological process through which epithelial cells lose their epithelial cobblestone phenotype and acquire fibroblastic and mesenchymal-like phenotypes These dramatic phenotypic changes involve disruption of intercellular junctions, replacement of apical-basal polarity with front to back polarity, and acquisition of more potent motile ability [8]. The stimulation of these signaling pathways results in the activation of numerous transcriptional factors, including snail (hereafter snail), snail2/slug, twist, ZEB1, ZEB2, hypoxia inducing factors (HIF), NF-κB, stat, stat and Foxo, thereby controlling the alterations in geneexpression patterns that underlie EMT [8,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
