TonEBP expression is essential in the IL-1β–induced migration and invasion of human A549 lung cancer cells

Lung cancer has the highest mortality rate among all cancers,in part because it readily metastasizes.The tumor microenvironment,comprising blood vessels,fibroblasts,immune cells,and macrophages[including tumor-associated macrophages(TAMs)],is closely related to cancer cell growth,migration,and invasion.TAMs secrete several cytokines,including interleukin(IL)-1β,which participate in cancer migration and invasion.p21-activated kinase 1(PAK1),an important signaling molecule,induces cell migration and invasion in several carcinomas.Tonicityresponsive enhancer-binding protein(TonEBP)is also known to participate in cancer cell growth,migration,and invasion.However,the mechanisms by which it increases lung cancer migration remain unclear.Therefore,in this study,we aimed to elucidate the mechanisms by which IL-1βand TonEBP affect lung cancer cell migration and invasion.We found that A549 cocultured-MΦ-secreted IL-1βinduced A549 cell migration and invasion via the PAK1 pathway.TonEBP deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1β–induced migration and invasion.PAK1 phosphorylation,which was promoted by IL-1β,was reduced when TonEBP was depleted.These results suggest that TonEBP plays an important role in IL-1βinduction and invasiveness of A549 cells via the PAK1 pathway.These findings could be valuable in identifying potential targets for lung cancer treatment.

Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathy via modulation of brain-derived neurotrophic factor expression

OBJECTIVE:Chemotherapeutic agents such as docetaxel(DTX)can trigger chemotherapy-induced peripheral neuropathy(CIPN),which is characterized by unbearable pain.This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation(LFMNS)on DTX-induced tactile hypersensitivity in mice.METHODS:To produce CIPN,DTX was administered intraperitoneally 4 times,once every 2 d,to male ICR mice.LFMNS was performed on the wrist area,and the pain response was measured using von Frey filaments on both hind paws.Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brainderived neurotrophic factor(BDNF).RESULTS:Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area.CONCLUSIONS:LFMNS might be an effective nonpharmaceutical option for treating patients suffering from CIPN via regulating the expression of peripheral and central BDNF.