Author of

• 28971

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  Lunch & Poster Display session (ID 58)

  • Event: ELCC 2019
  • Type: Poster Display session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1

  • 29007

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    40P - The metabolic phenotypes of non-small cell lung cancer cells in association with clinical treatment strategies (ID 224)

    12:30 - 13:00  |  Author(s): Tzu-Hung Hsiao
    • Abstract

    Background
    

    In 2011, metabolic reprogramming was defined as one of the cancer hallmarks, and several drugs targeting cancer metabolism have been developed as anti-cancer drugs. To improve medication efficiency of these anti-metabolic drugs, we tried to sub-classify non-small cell lung cancer (NSCLC) cells by their glycolytic dependency and treat them by targeting different metabolism-related proteins.

    a9ded1e5ce5d75814730bb4caaf49419 Methods
    

    We stratified NSCLC cells according to their Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR) measured by the Seahorse XF analyzer. Metformin, an inhibitor of mitochondrial respiratory complex I, was used as an example to measure the sensitivities of NSCLC cells in different metabolic subtypes to drugs targeting oxidative phosphorylation (OXPHOS) pathways.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    According to the OCR and ECAR, measured by the Seahorse XF analyser, NSCLC cells could be further separated into two metabolic subtypes, OXPHOS-dependent and glycolysis-dependent subtypes. We found that the OXPHOS-dependent subtype was sensitive to metformin, while the glycolysis-dependent subtype was resistant. To target the glycolysis-dependent subtype of NSCLC cells, monocarboxylate transporter 4 (MCT4), a proton-linked lactate transporter, was identified. MCT4 was highly expressed in the glycolysis-dependent subtype of NSCLC cells and its’ expression was important for these cells. When we knocked down the expression or blocked the function of MCT4, the proliferation of these cells was significantly inhibited.

    fd69c5cf902969e6fb71d043085ddee6 Conclusions
    

    In this report, we established a method to sub-classify NSCLC cells and predict the sensitivity of these cells to metformin. Besides, we identified MCT4 transporter as a druggable target to inhibit the proliferation of glycolysis-dependent subtype of NSCLC.

    b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
    

    The authors.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    Ministry of Science and Technology in Taiwan.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    All authors have declared no conflicts of interest.

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