Browsing by Author "Neugent, Michael L."
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Item The Distinct Metabolic Phenotype of Lung Squamous Cell Carcinoma Defines Selective Vulnerability to Glycolytic Inhibition(Springer Nature, 2018-08-20) Goodwin, Justin; Neugent, Michael L.; Lee, Shin Yup; Choe, Joshua H.; Choi, Hyunsung; Jenkins, Dana M. R.; Ruthenborg, Robin J.; Robinson, Maddox W.; Jeong, Ji Yun; Wake, Masaki; Abe, Hajime; Takeda, Norihiko; Endo, Hiroko; Inoue, Masahiro; Xuan, Zhenyu; Yoo, Hyuntae; Chen, Min; Ahn, Jung-Mo; Xuan, Zhenyu; Yoo, Hyuntae; Chen, Min; Ahn, Jung-Mo; Minna, John D.; Helke, Kristi L.; Singh, Pankaj K.; Shackelford, David B.; Kim, Jung-whan; Goodwin, Justin; Neugent, Michael L.; Lee, Shin Yup; Choe, Joshua H.; Choi, Hyunsung; Jenkins, Dana M. R.; Ruthenborg, Robin J.; Robinson, Maddox W.; Xuan, Zhenyu; Yoo, Hyuntae; Kim, Jung-whanAdenocarcinoma (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 F-18-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.Item A New Perspective on the Heterogeneity of Cancer Glycolysis(2018-10-22) Neugent, Michael L.; Goodwin, Justin; Sankaranarayanan, Ishwarya; Yetkin, Celal Emre; Hsieh, Meng-Hsiung; Kim, Jung-whan; Neugent, Michael L.; Sankaranarayanan, Ishwarya; Yetkin, Celal Emre; Hsieh, Meng-Hsiung; Kim, Jung-whanTumors are dynamic metabolic systems which highly augmented metabolic fluxes and nutrient needs to support cellular proliferation and physiological function. For many years, a central hallmark of tumor metabolism has emphasized a uniformly elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to extensive efforts of targeting glycolysis in human cancers. However, clinical attempts to target glycolysis and glucose metabolism have proven to be challenging. Recent advancements revealing a high degree of metabolic heterogeneity and plasticity embedded among various human cancers may paint a new picture of metabolic targeting for cancer therapies with a renewed interest in glucose metabolism. In this review, we will discuss diverse oncogenic and molecular alterations that drive distinct and heterogeneous glucose metabolism in cancers. We will also discuss a new perspective on how aberrantly altered glycolysis in response to oncogenic signaling is further influenced and remodeled by dynamic metabolic interaction with surrounding tumor-associated stromal cells.