bims-stacyt Biomed News
on Metabolism and the paracrine crosstalk between cancer and the organism
Issue of 2020–10–11
two papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Lipid Metabolism in Regulation of Macrophage Functions.
  2. From oxygen sensing to angiogenesis: Targeting the hypoxia signaling pathway in metastatic kidney cancer.
  1. Trends Cell Biol. 2020 Oct 06. pii: S0962-8924(20)30175-6. [Epub ahead of print]
    Lipid Metabolism in Regulation of Macrophage Functions.
    Jiawei Yan, Tiffany Horng.
      Macrophages are cells of the innate immune system that regulate the maintenance of tissue homeostasis, host defense during pathogen infection, and tissue repair in response to tissue injury. Recent studies indicate that macrophage functions are influenced by cellular metabolism, including lipid metabolism. Here, we review how macrophage lipid metabolism can be dynamically altered in different physiological and pathophysiological contexts and the key regulators involved. We also describe how alterations in lipid metabolism are integrated with the signaling pathways that specify macrophage functions, allowing for coordinated control of macrophage biology. Finally, we discuss how dysregulated lipid metabolism contributes to perturbed macrophage functions in settings such as atherosclerosis and pathogen infections.
    Keywords:  cholesterol metabolism; immunometabolism; lipid metabolism; macrophage activation; macrophage metabolism
    DOI:  https://doi.org/10.1016/j.tcb.2020.09.006
  2. Am J Health Syst Pharm. 2020 Oct 05. pii: zxaa308. [Epub ahead of print]
    From oxygen sensing to angiogenesis: Targeting the hypoxia signaling pathway in metastatic kidney cancer.
    Clement Chung.
       PURPOSE: This article summarizes examples of current and emerging therapies that target the hypoxia and angiogenesis signaling pathways in the clear cell type of renal cell cancer (RCC), with an emphasis on the hypoxia signaling pathway.
    SUMMARY: Mammalian cells transduce signals of decreased oxygen to hypoxia inducible factor (HIF), an intracellular heterodimer that mediates the adaptation of normal and tumor cells to oxygen deprivation. HIF is frequently overexpressed in cancer cells and is involved in the transcriptional activation of many genes essential for cell invasion, migration, survival, and angiogenesis (including vascular endothelial growth factor [VEGF]). Moreover, HIF confers resistance to cytotoxic chemotherapy and radiation therapy and is associated with poor prognosis in patients with cancer. Blocking the activity of HIF inhibits the expression of VEGF and oncogenic pathways, resulting in the inhibition of tumor growth. Interestingly, activation of oncogenes and/or inactivation of tumor suppressor genes (eg, the gene encoding von Hippel-Lindau [VHL] tumor suppressor protein) can activate tumorigenesis even with normal levels of oxygen, providing support for the notion that the HIF-VHL-VEGF axis is amenable to targeted therapies for the treatment of RCC. This article highlights the current understanding of the hypoxia signaling pathway and its relevance to RCC development. Pharmacologic agents targeting the hypoxia and angiogenesis signaling pathways are discussed.
    CONCLUSION: Development of novel therapeutic agents that target the hypoxia and angiogenesis signaling pathways holds promise in the management of metastatic clear cell RCC.
    Keywords:  MK-6482; angiogenesis; hypoxia; hypoxia inducible factor; kidney cancer; von Hippel-Lindau disease
    DOI:  https://doi.org/10.1093/ajhp/zxaa308
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