PMID- 37249337 OWN - NLM STAT- MEDLINE DCOM- 20230621 LR - 20240102 IS - 1745-7270 (Electronic) IS - 1672-9145 (Print) IS - 1672-9145 (Linking) VI - 55 IP - 5 DP - 2023 May 29 TI - NQO1/CPT1A promotes the progression of pancreatic adenocarcinoma via fatty acid oxidation. PG - 758-768 LID - 10.3724/abbs.2023066 [doi] AB - 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. FAU - Xu, Ran AU - Xu R AD - Inner Mongolia Minzu University, Tongliao 028000, China. AD - Key Laboratory of Pathobiology of High Frequency Oncology in Ethnic Minority Areas (Yanbian University), State Ethnic Affairs Commission, Yanji 133000, China. FAU - Liu, Ying AU - Liu Y AD - Key Laboratory of Pathobiology of High Frequency Oncology in Ethnic Minority Areas (Yanbian University), State Ethnic Affairs Commission, Yanji 133000, China. FAU - Ma, Liang AU - Ma L AD - Department of General Surgery, Siping Central People Hospital, Siping 136000, China. FAU - Sun, Yao AU - Sun Y AD - Department of General Surgery, Siping Central People Hospital, Siping 136000, China. FAU - Liu, Haifeng AU - Liu H AD - Department of General Surgery, Siping Central People Hospital, Siping 136000, China. FAU - Yang, Yang AU - Yang Y AD - Department of General Surgery, Siping Central People Hospital, Siping 136000, China. AD - Key Laboratory of Pathobiology of High Frequency Oncology in Ethnic Minority Areas (Yanbian University), State Ethnic Affairs Commission, Yanji 133000, China. FAU - Jin, Tiefeng AU - Jin T AD - Key Laboratory of Pathobiology of High Frequency Oncology in Ethnic Minority Areas (Yanbian University), State Ethnic Affairs Commission, Yanji 133000, China. FAU - Yang, Dawei AU - Yang D AD - Department of General Surgery, Siping Central People Hospital, Siping 136000, China. LA - eng PT - Journal Article PL - China TA - Acta Biochim Biophys Sin (Shanghai) JT - Acta biochimica et biophysica Sinica JID - 101206716 RN - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase) RN - 0 (Fatty Acids) RN - EC 1.6.5.2 (NQO1 protein, human) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) SB - IM MH - Humans MH - *Adenocarcinoma/genetics MH - Cell Line, Tumor MH - Carnitine O-Palmitoyltransferase/genetics/metabolism MH - *Pancreatic Neoplasms/genetics MH - Fatty Acids/metabolism MH - NAD(P)H Dehydrogenase (Quinone)/genetics PMC - PMC10281888 OTO - NOTNLM OT - CPT1A OT - NQO1 OT - PAAD OT - fatty acid oxidation OT - metastasis COIS- The authors declare that they have no conflict of interest. EDAT- 2023/05/30 13:07 MHDA- 2023/06/21 06:42 PMCR- 2023/05/29 CRDT- 2023/05/30 09:12 PHST- 2023/06/21 06:42 [medline] PHST- 2023/05/30 13:07 [pubmed] PHST- 2023/05/30 09:12 [entrez] PHST- 2023/05/29 00:00 [pmc-release] AID - 10.3724/abbs.2023066 [doi] PST - ppublish SO - Acta Biochim Biophys Sin (Shanghai). 2023 May 29;55(5):758-768. doi: 10.3724/abbs.2023066.