Inner Mongolia Minzu University, Tongliao 028000, China.
Key Laboratory of Pathobiology of High Frequency Oncology in Ethnic Minority Areas (Yanbian University), State Ethnic Affairs Commission, Yanji 133000, China.
Acta Biochim Biophys Sin (Shanghai). 2023 May 29;55(5):758-768. doi: 10.3724/abbs.2023066.
NQO1, a cytosolic enzyme, is closely related to the progression of cancers and poor outcome of cancer patients. However, the molecular biological mechanism of NQO1 tumorigenicity in pancreatic adenocarcinoma (PAAD) has not been clearly understood. In this study, we demonstrate the molecular mechanism of NQO1 in PAAD proliferation, metastasis and fatty acid oxidation (FAO). Multiple databases and western blot analysis show that NQO1 is overexpressed in PAAD and associated with lymph node metastasis and shorter survival. Furthermore, and experiments reveal that overexpression of NQO1 improves tumor growth, metastasis and FAO in PAAD. Mechanistically, NQO1 is able to bind to carnitine palmitoyltransferase 1A (CPT1A), a key enzyme controlling FAO. Therefore, Co-IP and a series of rescue experiments demonstrate that NQO1 promotes PAAD progression via CPT1A-mediated FAO. Our findings identify CPT1A-dependent FAO as an essential metabolic pathway for NQO1 to promote the PAAD process. Targeting the NQO1/CPT1A/FAO axis in PAAD to attenuate proliferation and dissemination is a potential approach to promote a better antitumour effect and improve patient outcomes.
NQO1 是一种细胞溶质酶，与癌症的进展和癌症患者的不良预后密切相关。然而，NQO1 在胰腺导管腺癌 (PAAD) 中的致癌分子生物学机制尚不清楚。在这项研究中，我们证明了 NQO1 在 PAAD 增殖、转移和脂肪酸氧化 (FAO) 中的分子机制。多个数据库和 Western blot 分析表明，NQO1 在 PAAD 中过表达，并与淋巴结转移和更短的生存时间相关。此外，过表达 NQO1 实验揭示了 NQO1 可改善 PAAD 中的肿瘤生长、转移和 FAO。从机制上讲，NQO1 能够与肉碱棕榈酰转移酶 1A（CPT1A）结合，CPT1A 是控制 FAO 的关键酶。因此，Co-IP 和一系列挽救实验表明，NQO1 通过 CPT1A 介导的 FAO 促进 PAAD 进展。我们的研究结果确定了 CPT1A 依赖性 FAO 作为 NQO1 促进 PAAD 进程的必需代谢途径。针对 PAAD 中的 NQO1/CPT1A/FAO 轴以减弱增殖和扩散是促进更好的抗肿瘤作用和改善患者预后的一种潜在方法。
