Abstract
Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.
Highlights
Esophageal squamous cell carcinoma (ESCC) an extremely common gastrointestinal malignancy that carries with its high morbidity and mortality
Results based on the TCGA database showed that Aurora A was highly expressed in human ESCC tissues (Fig. 1A), and that high expression of Aurora A correlated to a high ESCC grade (Fig. 1B)
RT-PCR results showed that mRNA levels of Aurora A and ubiquitin specific peptidase 3 (USP3) were highly expressed in ESCC compared to adjacent tissues (Fig. 1E and F)
Summary
Esophageal squamous cell carcinoma (ESCC) an extremely common gastrointestinal malignancy that carries with its high morbidity and mortality. It is currently the 9th cause of highest global cancer incidence and the 6th cause of highest total mortality rate. In 1990, ESCC was the 7th largest cancer, climbing up the ranks to the 6th in 2013. An aging population along with a massive population growth are drivers of the increased occurrence of ESCC [8, 9]. Squamous cell carcinoma and adenocarcinoma are the main ESCC pathological subtypes.
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