Abstract 4362: Glucose transporter 1 regulates cell glycolysis and proliferation in gastrointestinal stromal tumor and its clinicopathological significance

Abstract

Abstract Background: The unique features that cancer cells prefer glycolysis rather than mitochondrial respiration despite of the presence of oxygen have been a potential target for cancer treatment. GIST is well-known as to demonstrate intense metabolic activity and avid glucose uptake on 18F-FDG PET scanning. In this study, we focused on glucose transporter 1 (GLUT 1), a key glycolytic enzyme which plays critical roles in several cancer type. The aim of this study was to examine the clinicopathological significance of GLUT1 expression in GIST and to characterize the molecular mechanism of cell glycolysis and proliferation by GIST cell. Methods: We determined the expression level of GLUT1 in 65 GIST cases, correlated those values with clinicopathological features. Furthermore, we investigated that the alteration of GLUT1 can influence on glycolysis, cell proliferation, and cell cycle distribution by extracellular flux analyzer, CCK-8 assay and flow cytometry, respectively in GIST cell in vitro. Results: Fifty-one (78.5%) cases were placed in the high GLUT1 expression group. In the high GLUT1 expression group, tumor size was significantly larger compared to the low GLUT1 expression group (P=0.02). There are significantly more high-risk cases by modified-Fletcher classification in GLUT1 expression group (P< 0.01). The patients with high GLUT1 expression significantly exhibited a higher SUVmax value (P< 0.01). Compared with the low GLUT1 expression group, the high expression group showed a significantly poorer prognosis in terms of recurrence-free survival. In vitro, GLUT1-specific siRNA suppressed cell proliferation and led to increase in G1 phase arrest. Also, knockdown of GLUT1 cells reduced glycolysis as a function of ECAR by extracellular flux analyzer. Conclusion: We showed that GLUT1 plays a critical role in GIST by regulating glycolysis and proliferation. Our study suggests that glucose transporter can be a novel target of anticancer therapeutics mediating glucose metabolism in GIST. Citation Format: Masaaki Iwatsuki, Hiroshi Sawayama, Daisuke Kuroda, Yuki Koga, Kohei Yamashita, Kazuto Harada, Shiro Iwagami, Kojiro Eto, Takatsugu Ishimoto, Yoshifumi Baba, Naoya Yoshida, Jaffer A. Ajani, Hideo Baba. Glucose transporter 1 regulates cell glycolysis and proliferation in gastrointestinal stromal tumor and its clinicopathological significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4362.