NQO1 promotes an aggressive phenotype in hepatocellular carcinoma via amplifying ERK‐NRF2 signaling |
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| Authors: | Yun Yang Jie Zheng Mengchao Wang Jin Zhang Tao Tian Zhiheng Wang Shengxian Yuan Lei Liu Peng Zhu Fangming Gu Siyuan Fu Yunfeng Shan Zeya Pan Weiping Zhou |
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| Affiliation: | 1. The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China;2. Department of Intervention, First Affiliated Hospital, Wenzhou Medical University, Zhejiang, China;3. Department of Hepatobiliary Surgery, First Affiliated Hospital, Wenzhou Medical University, Zhejiang, China |
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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 showed that high levels of NQO1 expression frequently exist in HCC with an obvious cancer‐specific pattern. Patients with NQO1‐high tumors are significantly associated with poor survival outcomes and serve as independent predictors. 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 block of ERK and NRF2 signaling generated stronger growth inhibition compared with any single block, especially for HCC with high‐NQO1. Therefore, NQO1 is a potential biomarker for HCC early diagnosis and prognosis prediction, and also attractive for cancer‐specific targets for HCC treatment. |
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| Keywords: | hepatocellular carcinoma NQO1 NRF2 prognosis tumorigenesis |
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