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The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition

Author

Listed:
  • Justin Goodwin

    (The University of Texas at Dallas)

  • Michael L. Neugent

    (The University of Texas at Dallas)

  • Shin Yup Lee

    (The University of Texas at Dallas
    School of Medicine, Kyungpook National University)

  • Joshua H. Choe

    (The University of Texas at Dallas
    St Mark’s School of Texas)

  • Hyunsung Choi

    (The University of Texas at Dallas)

  • Dana M. R. Jenkins

    (The University of Texas at Dallas)

  • Robin J. Ruthenborg

    (The University of Texas at Dallas)

  • Maddox W. Robinson

    (The University of Texas at Dallas)

  • Ji Yun Jeong

    (School of Medicine, Kyungpook National University)

  • Masaki Wake

    (The University of Tokyo)

  • Hajime Abe

    (The University of Tokyo)

  • Norihiko Takeda

    (The University of Tokyo)

  • Hiroko Endo

    (Osaka International Cancer Institute)

  • Masahiro Inoue

    (Osaka International Cancer Institute)

  • Zhenyu Xuan

    (The University of Texas at Dallas
    The Center for Systems Biology, The University of Texas at Dallas)

  • Hyuntae Yoo

    (The University of Texas at Dallas)

  • Min Chen

    (The University of Texas at Dallas)

  • Jung-Mo Ahn

    (The University of Texas at Dallas)

  • John D. Minna

    (Hamon Center for Therapeutic Oncology Research, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center)

  • Kristi L. Helke
  • Pankaj K. Singh

    (The Eppley Institute for Cancer and Allied Diseases, Cell Biology and Anatomy, University of Nebraska Medical Center)

  • David B. Shackelford

    (David Geffen, School of Medicine, University of California)

  • Jung-whan Kim

    (The University of Texas at Dallas)

Abstract

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.

Suggested Citation

  • Justin Goodwin & Michael L. Neugent & Shin Yup Lee & Joshua H. Choe & Hyunsung Choi & Dana M. R. Jenkins & Robin J. Ruthenborg & Maddox W. Robinson & Ji Yun Jeong & Masaki Wake & Hajime Abe & Norihiko, 2017. "The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition," Nature Communications, Nature, vol. 8(1), pages 1-16, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15503
    DOI: 10.1038/ncomms15503
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