bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2019‒06‒30
two papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge


  1. Semin Cell Dev Biol. 2019 Jun 22. pii: S1084-9521(18)30186-1. [Epub ahead of print]
    Majem B, Nadal E, Muñoz-Pinedo C.
      Lung cancer is the main cause of cancer death worldwide. Non-Small Cell Lung Carcinoma (NSCLC) is the most common subtype of lung cancer, and the prognosis of NSCLC patients in advanced stages is still very poor. Given the need for new therapies, the metabolism of NSCLC has been widely studied in the past two decades to identify vulnerabilities that could be translated into novel anti-metabolic therapeutic approaches. A number of studies have highlighted the role of glucose and mitochondrial metabolism in the development of NSCLC. The metabolic properties of lung tumors have been characterized in detail in vivo, and they include high glucose and lactate use and high heterogeneity regarding the use of nutrients and mitochondrial pathways. This heterogeneity has also been observed in patients infused with labeled nutrients. We will summarize here the knowledge about the use of amino acids, fatty acids and carbohydrates in NSCLC that could lead to new combination treatments.
    Keywords:  Non-Small Cell Lung Carcinoma; cancer metabolism; glucose; mitochondria
    DOI:  https://doi.org/10.1016/j.semcdb.2019.06.004
  2. Nature. 2019 Jun 26.
    Wang X, Liu R, Zhu W, Chu H, Yu H, Wei P, Wu X, Zhu H, Gao H, Liang J, Li G, Yang W.
      Cancer metastasis is the primary cause of morbidity and mortality, and accounts for up to 95% of cancer-related deaths1. Cancer cells often reprogram their metabolism to efficiently support cell proliferation and survival2,3. However, whether and how those metabolic alterations contribute to the migration of tumour cells remain largely unknown. UDP-glucose 6-dehydrogenase (UGDH) is a key enzyme in the uronic acid pathway, and converts UDP-glucose to UDP-glucuronic acid4. Here we show that, after activation of EGFR, UGDH is phosphorylated at tyrosine 473 in human lung cancer cells. Phosphorylated UGDH interacts with Hu antigen R (HuR) and converts UDP-glucose to UDP-glucuronic acid, which attenuates the UDP-glucose-mediated inhibition of the association of HuR with SNAI1 mRNA and therefore enhances the stability of SNAI1 mRNA. Increased production of SNAIL initiates the epithelial-mesenchymal transition, thus promoting the migration of tumour cells and lung cancer metastasis. In addition, phosphorylation of UGDH at tyrosine 473 correlates with metastatic recurrence and poor prognosis of patients with lung cancer. Our findings reveal a tumour-suppressive role of UDP-glucose in lung cancer metastasis and uncover a mechanism by which UGDH promotes tumour metastasis by increasing the stability of SNAI1 mRNA.
    DOI:  https://doi.org/10.1038/s41586-019-1340-y