Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways

Tianxiang Wang; Min Zhang; Xinyu Gong; Wanjing Chen; Ying Peng; Chenzhong Liao; Hongmei Xu; Qingshan Li; Guodong Shen; Huirong Ren; Yaxin Zhu; Baotong Zhang; Jiali Mao; Lingling Wei; Yuanli Chen; Xiaoxiao Yang

doi:10.1016/j.isci.2024.109741

Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways

iScience. 2024 Apr 12;27(5):109741. doi: 10.1016/j.isci.2024.109741. eCollection 2024 May 17.

Authors

Tianxiang Wang¹, Min Zhang¹, Xinyu Gong¹, Wanjing Chen², Ying Peng¹, Chenzhong Liao¹, Hongmei Xu¹, Qingshan Li¹, Guodong Shen³, Huirong Ren³, Yaxin Zhu⁴, Baotong Zhang⁵, Jiali Mao⁶, Lingling Wei¹, Yuanli Chen¹, Xiaoxiao Yang¹

Affiliations

¹ Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, College of Food and Biological Engineering, Hefei University of Technology, Hefei 230000, China.
² Department of General Surgery, The Second Affiliated Hospital, Anhui Medical University, Hefei 230000, China.
³ Department of Geriatrics, The First Affiliated Hospital of University of Science and Technology of China, Gerontology Institute of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230000, China.
⁴ Institute for International Health Professions Education and Research, China Medical University, Shenyang 110000, China.
⁵ Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, China.
⁶ Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230000, China.

Abstract

Pancreatic cancer (PC) is a lethal disease and associated with metabolism dysregulation. Nogo-B is related to multiple metabolic related diseases and types of cancers. However, the role of Nogo-B in PC remains unknown. In vitro, we showed that cell viability and migration was largely reduced in Nogo-B knockout or knockdown cells, while enhanced by Nogo-B overexpression. Consistently, orthotopic tumor and metastasis was reduced in global Nogo knockout mice. Furthermore, we indicated that glucose enhanced cell proliferation was associated to the elevation expression of Nogo-B and nuclear factor κB (NF-κB). While, NF-κB, glucose transporter type 1 (GLUT1) and sterol regulatory element-binding protein 1 (SREBP1) expression was reduced in Nogo-B deficiency cells. In addition, we showed that GLUT1 and SREBP1 was downstream target of NF-κB. Therefore, we demonstrated that Nogo deficiency inhibited PC progression is regulated by the NF-κB/GLUT1 and SREBP1 pathways, and suggested that Nogo-B may be a target for PC therapy.

Keywords: Cancer; Cell biology; Molecular biology.