NQO1/CPT1A promotes the progression of pancreatic adenocarcinoma via fatty acid oxidation

Sep 24, 2026

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NQO1, a cytosolic enzyme linked to cancer progression and poor outcomes, has unclear molecular mechanisms in pancreatic adenocarcinoma (PAAD). This study shows NQO1 is overexpressed in PAAD and correlates with lymph node metastasis and shorter survival through database mining and western blot analysis. Functional assays demonstrate that NQO1 enhances tumor growth, metastasis, and fatty acid oxidation (FAO). Mechanistically, NQO1 binds CPT1A, and Co-IP plus rescue experiments confirm that NQO1 promotes PAAD progression via CPT1A-mediated FAO, highlighting a CPT1A-dependent metabolic pathway and a potential therapeutic target.

LanguageEnglish

CategoryResearch & Report

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Pages11

Reading Time28 min

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Abstract

Introduction

Materials and Methods

Original Article NQO1/CPT1A promotes the progression of pancreatic adenocarcinoma via fatty acid oxidation Ran Xu2,3, Ying Liu3, Liang Ma 1, Yao Sun1, Haifeng Liu 1, Yang Yang 1,3, *, Tiefeng Jin3, *, and Dawei Yang 1, * 1 Department of General Surgery, Siping Central People Hospital, Siping 136000, China, 2 Inner Mongolia Minzu University, Tongliao 028000, China, and 3 Key Laboratory of Pathobiology of High Frequency Oncology in Ethnic Minority Areas (Yanbian University), State Ethnic Affairs Commission, Yanji 133000, China *Correspondence address. Tel: +86-433-2435056; E-mail: [yangyang@ybu.edu.cn](yangyang@ybu.edu.cn) (Y.Y. ) / E-mail: [jintf@ybu.edu.cn](jintf@ybu.edu.cn) (T.J. ) / E-mail: [873770207@qq.com](873770207@qq.com) (D.Y. ) Received 22 August 2022 Accepted 8 December 2022 Abstract 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, in vitro and in vivo 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. Key words NQO1, PAAD, metastasis, fatty acid oxidation, CPT1A Introduction Pancreatic adenocarcinoma (PAAD) is the third leading cause of cancer-related death, with a five-year survival rate of approximately 11% [1] . Although multiple therapeutic strategies, such as immunotherapy and targeted therapies, have been tried to improve the survival of PAAD patients, the effect is still limited [2,3] . This may be partly due to the complexity and heterogeneity of PAAD. Therefore, the exploration of a promising biomarker that regulates the biological dynamics and behavior of PAAD will contribute remarkably to optimizing treatment. The gene of NAD(P)H:quinone oxidoreductase-1 (NQO1), also known as DT diaphorase, is located on chromosome 16q22 and consists of six exons and five introns [4,5] . It uses NADH or NADPH as a substrate to catalyze the two-electron reduction of quinine to its hydroquinone form, directly blocking quinone to hydroquinone [6] . In addition, more reports have found that NQO1 is closely related to clinical significance and molecular mechanisms in different malignant tumors [7] . Jiang et al. [8] found that the expression of NQO1 protein in gastric cancer tissue is higher than that in normal gastric tissue and is closely related to the patients’ tumor stage and age. Hirose et al. [9] found that the positive expression of NQO1 in colorectal and liver metastatic tumor cells may be an important factor for poor prognosis after hepatectomy. Yang et al. [10] revealed that the NQO1/PKLR axis promotes lymph node (LN) metastasis and breast cancer progression by regulating glycolytic reprogramming. Meanwhile, NQO1 could promote tumor formation by regulating the process of glucose metabolism [11] . Previous studies have revealed that the high expression of NQO1 is positively correlated with glucose metabolism and tumor progression. However, the relationship between NQO1 and the metabolic mechanism of PAAD progression has not yet been reported.

FAQs

Why is CPT1A important in the NQO1 mechanism?

NQO1 binds to CPT1A, a key enzyme controlling FAO. Co-IP and rescue experiments support that NQO1 drives PAAD progression through CPT1A-mediated FAO.

Sep 24, 2026

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