bims-stacyt Biomed News
on Metabolism and the paracrine crosstalk between cancer and the organism
Issue of 2024–11–10
two papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Hypoxia-Inducible Factor 1-Alpha (HIF-1α) and Cancer: Mechanisms of Tumor Hypoxia and Therapeutic Targeting.
  2. Overexpression of FBP1 enhances dendritic cell activation and maturation by inhibiting glycolysis and promoting the secretion of IL33 in lung adenocarcinoma.
  1. Cureus. 2024 Oct;16(10): e70700
    Hypoxia-Inducible Factor 1-Alpha (HIF-1α) and Cancer: Mechanisms of Tumor Hypoxia and Therapeutic Targeting.
    Mohd Basheeruddin, Sana Qausain.
      Hypoxia-inducible factor 1-alpha (HIF-1α) is necessary for cells to adapt to low oxygen levels often present in the tumor microenvironment. HIF-1α triggers a transcriptional program that promotes invasion, angiogenesis, metabolic reprogramming, and cell survival when it is active in hypoxic environments. These processes together lead to the growth and spread of tumors. This review article examines the molecular mechanisms by which HIF-1α contributes to tumor progression, including its regulation by oxygen-dependent and independent pathways, interactions with oncogenic signaling networks, and impact on the tumor microenvironment. Additionally, we explore current therapeutic strategies targeting HIF-1α, such as small molecule inhibitors, RNA interference, and immunotherapy approaches. Understanding the multifaceted roles of HIF-1α in cancer biology not only elucidates the complexities of tumor hypoxia but also opens avenues for developing novel and more effective cancer therapies.
    Keywords:  angiogenesis; cancer progression; hif-1α; immunotherapy; rna interference; small molecule inhibitors; therapeutic targeting
    DOI:  https://doi.org/10.7759/cureus.70700
  2. Biochim Biophys Acta Mol Basis Dis. 2024 Oct 30. pii: S0925-4439(24)00553-2. [Epub ahead of print]1871(1): 167559
    Overexpression of FBP1 enhances dendritic cell activation and maturation by inhibiting glycolysis and promoting the secretion of IL33 in lung adenocarcinoma.
    Chunwei Li, Lili Zhu, Yaqi Yang, Tengfei Zhang, Chengxin Chen, Yixing Zhang, Wenxuan Ji, Xiaoran Duan, Wenhua Xue, Lifeng Li, Jie Zhao.
      Fructose 1,6-diphosphatase 1 (FBP1) is an enzyme involved in gluconeogenesis and glycolysis inhibition. Dendritic cells (DCs) are antigen-presenting cells, and antigens presented to T cells activate the immune response. FBP1 inhibits the development of several tumors, and high FBP1 expression inhibits the proliferation, migration, and invasion of lung cancer cells. However, the mechanism through which FBP1 mediates the tumor immune microenvironment is unclear. This study mainly analyzed the role of FBP1 in regulating the function of DCs through metabolic reprogramming and immune microenvironment using in vitro and in vivo experiments. The positive association of FBP1 with DCs was found by bioinformatic analysis. The in vitro experiments revealed that the extracellular acidification rate and lactate level were lower in the FBP1 overexpression cells than in the control cells and that the lower lactate level reduced the inhibition of DC function. In addition, high FBP1 expression promoted the secretion of IL33 by activating the cGAS/STING/NF-κB/IL33 pathway, which was identified and verified via high-throughput sequencing and in vitro experiments. FBP1 activated the cGAS/STING pathway by increasing the degree of DNA damage, as revealed by the level of γH2AX and comet assay. IL33 enhanced the expression of the DC costimulatory molecules CD86 and HLA-DR as well as that of the functional factor IL-1β. The results demonstrated that FBP1 promoted the activation and maturation of DCs by inhibiting glycolysis and promoting the secretion of IL33 as well as by further activating the function of CD8+T cells. Finally, the humanized immune system mouse models confirmed the above role of FBP1. Thus, FBP1 may serve as a new target to cure lung adenocarcinoma, and IL33 may improve the efficiency of immune therapy in lung adenocarcinoma.
    Keywords:  Dendritic cells; Fructose 1,6-diphosphatase 1; IL33; Lactate; Lung adenocarcinoma; cGAS/STING
    DOI:  https://doi.org/10.1016/j.bbadis.2024.167559
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