NAD[P]H:quinone oxidoreductase 1 (NQO1) regulates cell fate decisions in response to stress. Oxidative stress supports cancer maintenance and progression. Previously we showed that knockdown of NQO1 (NQO1low) prostate cancer cells upregulate pro-inflammatory cytokines and survival under hormone-deprived conditions. Here, we tested the ability of NQO1low cells to form tumors. We found NQO1low cells form aggressive tumors compared with NQO1high cells. Biopsy specimens and circulating tumor cells showed biochemical recurrent prostate cancer was associated with low NQO1. NQO1 silencing was sufficient to induce SMAD-mediated TGFβ signaling and mesenchymal markers. TGFβ treatment decreased NQO1 levels and induced molecular changes similar to NQO1 knockdown cells. Functionally, NQO1 depletion increased migration and sensitivity to oxidative stress. Collectively, this work reveals a possible new gatekeeper role for NQO1 in counteracting cellular plasticity in prostate cancer cells. Further, combining NQO1 with TGFβ signaling molecules may serve as a better signature to predict biochemical recurrence.

中文翻译：

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NAD [P] H：醌氧化还原酶1的减弱通过增强的TGFβ信号传导加剧了前列腺癌和肿瘤细胞的可塑性。

NAD [P] H：醌氧化还原酶1（NQO1）调节细胞命运决定应对压力。氧化应激支持癌症的维持和进展。先前我们显示，敲低NQO1（NQO1low）前列腺癌细胞会在激素剥夺的条件下上调促炎性细胞因子和存活率。在这里，我们测试了NQO1low细胞形成肿瘤的能力。我们发现NQO1low细胞与NQO1high细胞形成侵袭性肿瘤。活检标本和循环中的肿瘤细胞显示前列腺癌的生化复发与低NQO1有关。NQO1沉默足以诱导SMAD介导的TGFβ信号传导和间充质标记。TGFβ处理降低了NQO1水平，并诱导了类似于NQO1敲低细胞的分子变化。从功能上讲，NQO1耗竭增加了迁移和对氧化应激的敏感性。总的来说，这项工作揭示了NQO1在抵消前列腺癌细胞中细胞可塑性方面可能发挥的新看门人作用。此外，将NQO1与TGFβ信号分子结合可以更好地预测生化复发。