The head and neck cancer (HNC) means the cancer which emerges in the oral cavity, tongue, nasopharynx, hypopharynx, oropharynx, and larynx [1]. Each HNC subtype has a characteristic etiology, treatment, epidemiology [2]. HNC is a critical contributor to cancer incidence and mortality. Moreover, in China roughly 225,100 novel patients and 77,500 deaths were diagnosing each year [3]. It has a 5 years’ survival rate below 65% since most patients were diagnosed in terminal cancer on account of less symptoms during the early stages of HNC tumorigenesis [4]. Molecular biomarkers have become accepted as predictors of prognosis or of targeted treatment for HNC patients [5], [6]. Thereby, it is indispensable to identify these potential crucial biomarkers concerning the HNC initiation and progression, to improve diagnosis and prognosis.

Urokinase-Type Plasminogen Activator (PLAU) proteinase belongs to the S1 serine peptidase of the Plasminogen Activator (PA) family and participates in plasminogen transformation to plasmin [7], [8]. Through direct binding to the receptor or indirectly binding to plasmin, PLAU activates MAPK, the JAT-STAT signal pathway, and focal adhesion kinase systems [9]. Recent evidence illustrates the important PLAU function of initiating and developing cancers containing breast cancer [10], colorectal cancer [11], and esophageal cancer [12]. PLAU expression was capable of acting as one therapeutic target or prognostic biomarker in breast cancer [13], non-small cell lung cancer [14], and gastric cancer [7].

PLAU is also been considered a precise diagnostic and prognostic biomarker of head and neck squamous cell carcinoma (HNSCC) based upon the comprehensive analysis on bioinformation [15]. Sepiashvili et al.[16] claimed that PLAU showed high tumor expression, which was related to poor disease-free survival (DFS) and increased risk of HNSCC progress. Li et al. [17] revealed by means of univariate and multivariate Cox analysis, that PLAU could serve as an isolated index in HNSCC prognosis. Recently, Chen et al. [18] reported that PLAU facilitated cell proliferation and epithelial-mesenchymal transition (EMT) in HNSCC with CAL21 cell.

Above studies suggested that PLAU overexpression was involved in the progression of malignant cancer via regulating various signaling pathways, while its significance in HNC remain to be determined. Here we explored the influence and downstream molecular events of PLAU on HNC cells Fadu and Tu686, and identified the PLAU/STAT3 axis as a possible therapeutic target for HNC therapy.