iScience (May 2024)

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

Journal volume & issue
Vol. 27, no. 5
p. 109741

Abstract

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Summary: 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.

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