bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2020‒06‒14
four papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge


  1. J Cell Mol Med. 2020 Jun 09.
    Feng S, Zhang L, Liu X, Li G, Zhang B, Wang Z, Zhang H, Ma H.
      AMP-activated protein kinase (AMPK) serves as a "supermetabolic regulator" that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non-small-cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up-regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK-induced metabolism can promote epithelial-mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.
    Keywords:  AMPK; epithelial-mesenchymal transition; lung cancer; metabolism
    DOI:  https://doi.org/10.1111/jcmm.15410
  2. Biomolecules. 2020 Jun 05. pii: E868. [Epub ahead of print]10(6):
    Martinez CA, Scafoglio C.
      Increased glucose uptake is a known hallmark of cancer. Cancer cells need glucose for energy production via glycolysis and the tricarboxylic acid cycle, and also to fuel the pentose phosphate pathway, the serine biosynthetic pathway, lipogenesis, and the hexosamine pathway. For this reason, glucose transport inhibition is an emerging new treatment for different malignancies, including lung cancer. However, studies both in animal models and in humans have shown high levels of heterogeneity in the utilization of glucose and other metabolites in cancer, unveiling a complexity that is difficult to target therapeutically. Here, we present an overview of different levels of heterogeneity in glucose uptake and utilization in lung cancer, with diagnostic and therapeutic implications.
    Keywords:  cancer; glucose metabolism; glucose transport; lung cancer; tumor heterogeneity
    DOI:  https://doi.org/10.3390/biom10060868
  3. Cell Death Dis. 2020 Jun 08. 11(6): 437
    Shangguan H, Feng H, Lv D, Wang J, Tian T, Wang X.
      Growing evidence has highlighted the roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC), however, their roles in NSCLC glycolysis remains poorly understood. CircRNAs microarray profiles discovered a novel exon-derived circRNA, circSLC25A16 (hsa_circ_0018534), in NSCLC tissue samples. In NSCLC samples, high-expression of circSLC25A16 was associated with unfavorable prognosis. Cellular experiments revealed that circSLC25A16 accelerated the glycolysis and proliferation of NSCLC cells. Besides, circSLC25A16 knockdown repressed the in vivo growth by xenograft assays. RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that circSLC25A16 and miR-488-3p were both located in cytoplasm. Mechanistic experiments demonstrated that circSLC25A16 interacts with miR-488-3p/HIF-1α, which activates lactate dehydrogenase A (LDHA) by facilitating its transcription. Collectively, present research reveals the crucial function of circSLC25A16 on NSCLC glycolysis through miR-488-3p/HIF-1α/LDHA, suggesting the underlying pathogenesis for NSCLC and providing a therapeutic strategy for precise treatment.
    DOI:  https://doi.org/10.1038/s41419-020-2635-5
  4. World J Clin Cases. 2020 May 26. 8(10): 1916-1922
    Zhou YY, Du X, Tang JL, Wang QP, Chen K, Shi BM.
      BACKGROUND: The elevation of plasma von Willebrand factor (vWF) has been proposed to be a predictor of lung cancer. Type 2 diabetes mellitus (T2DM) causes endothelial activation, resulting in the secretion of vWF. However, the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIM: To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ (AIS).
    METHODS: This study enrolled 43 patients with T2DM combined with lung AIS (T2DM + AIS group), 43 patients with T2DM alone (T2DM group), 43 patients with lung AIS alone (AIS group), and 43 healthy volunteers (control group). The serum levels of vWF, insulin-like growth factor 1, and insulin-like growth factor binding protein 3 were determined. Multiple linear stepwise regression was performed to determine the correlations among variables.
    RESULTS: Serum concentration of vWF in the T2DM + AIS group was significantly higher than those in the T2DM, AIS, and control groups (P < 0.05). Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group (P < 0.05). There was no significant difference in serum vWF level between the T2DM and AIS groups. In the T2DM + AIS group, serum vWF was independently associated and positively correlated with serum levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 (P < 0.05).
    CONCLUSION: Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.
    Keywords:  Adenocarcinoma in situ; Correlation; Early diagnosis; Type 2 diabetes mellitus; von Willebrand factor
    DOI:  https://doi.org/10.12998/wjcc.v8.i10.1916