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Αλέξανδρος Γ. Σφακιανάκης

Sunday, November 22, 2020

NQO1 promotes an aggressive phenotype in hepatocellular carcinoma via amplifying ERK‐NRF2 signaling

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Abstract

Patients with hepatocellular carcinoma (HCC) are usually diagnosed at the later stages and have poor survival outcomes. New molecules are urgently needed for the prognostic predication and individual treatment. Our study shows that the high levels of NQO1 expression are frequently existed in HCC with obvious cancer‐specific pattern. The patient with NQO1‐high tumors was significantly associated with poor survival outcomes and served as an independent predictor. Functional experiments showed that NQO1 promotes the growth and aggressiveness of HCC in both in vitro and in vivo models, and the underlying mechanism involved NQO1‐derived amplification of ERK/P38‐NRF2 signaling. Combined blockage of ERK and NRF2 signaling generated the stronger growth inhibition than any single blockage, especially for HCC with high‐NQO1. Therefore, NQO1 is a potential biomarker for HCC early diagnosis and prognosis prediction, and also attractive cancer‐specific targets for HCC treatment.

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