PLAU contributes to the development of cholangiocarcinoma via activating NF‐κB signaling pathway

Abstract

Cholangiocarcinoma (CCA) is a type of epithelial cancer with poor outcomes and late diagnosis. Accumulating evidence has demonstrated the promoting role of plasminogen activator, urokinase (PLAU) in several tumor types, while its function in CCA is largely unknown. The expression of PLAU in CCA was determined by data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database and further confirmed in human tissues using immunohistochemical (IHC) staining. Moreover, PLAU‐silencing CCA cell models were constructed for subsequent functional assays in vitro and in vivo. PLAU expression in CCA was significantly higher than that in normal tissues. High PLAU expression was positively correlated with poor patients' survival. PLAU knockdown remarkably suppressed proliferation and migration of CCA cells, whereas enhanced apoptosis. Consistently, tumor growth in mice injected with PLAU‐silencing CCA cells was also impaired. Furthermore, we revealed that the activation of NF‐κB signaling was required for PLAU‐induced malignant phenotypes of CCA cells. Inhibiting the high expression of PLAU in CCA may be a potential entry point for targeted therapy in CCA patient.

Plasminogen activator urokinase interacts with the fusion protein and antagonizes the growth of Peste des petits ruminants virus

“…RLRs can collect specific intracellular junction proteins to initiate and activate signaling pathways such as NF-κB to control the transcription of genes encoding IFN-I and other inflammatory cytokines to inhibit virus replication ( 28 ). A previous study found that human PLAU could activate the NF-κB signaling pathway and participate in the development of bile duct cancer ( 20 ). We found high homology between human and goat PLAU using sequence alignment and investigated whether goat PLAU was involved in RLR-mediated signaling.…”

“…In the IFN system, this function is mainly mediated by IFN-I. Human PLAU has been shown to activate inflammatory responses in the NF-κB pathway in previous studies, while RIG-I or MDA5 signaling pathways have been shown to induce NF-κB or IRF3-mediated IFN-I production after viral stimulation, and IFN-I activates the JAK-STAT signaling pathway ( 20 , 37 , 38 ). Therefore, we suspected that goat PLAU influenced PPRV replication by promoting IFN-I.…”

“…After binding to uPAR on the cell surface, human PLAU can activate tyrosine and serine/threonine kinases in the cell and the corresponding cell signal transduction pathway, thereby causing chemotaxis ( 19 ). Recent studies have found that human PLAU can activate the NF-κB signaling pathway and participate in the development of cholangiocarcinoma ( 20 ).…”

PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1

“…PLAU has been documented to interact with GLIPR1 to activate EGFR signaling, consequently preventing from cigarette smoke-induced inflammatory response and airway damage [ 19 ]. PLAU shows the ability to activate NF-κB signaling to drive the development of cholangiocarcinoma [ 20 ]. PLAU is upregulated in lung cancer and can promote lung cancer cell invasion [ 21 , 22 ].…”