OncoTargets and Therapy (May 2021)
Effect of GLUT1 Inhibition and Autophagy Modulation on the Growth and Migration of Laryngeal Carcinoma Stem Cells Under Hypoxic and Low-Glucose Conditions
Abstract
Xiao-Hong Chen,1 Jia Liu,2 Jiang-Tao Zhong,2 Shui-Hong Zhou,2 Jun Fan3 1Department of Otolaryngology, The Second Hospital of Jiaxing (The Second Affiliated Hospital, Jiaxing University), Jiaxing City, Zhejiang Province, 314000, People’s Republic of China; 2Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaCorrespondence: Shui-Hong ZhouDepartment of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou City, 310003, People’s Republic of ChinaTel +86-571-87236894Fax +86-571-87236895Email [email protected]: Enhanced glucose uptake and autophagy are means by which cells adapt to stressful microenvironments. In this study, we investigated the roles of glucose transporter-1 (GLUT-1) and autophagy in laryngeal carcinoma stem cells under hypoxic and low-glucose conditions.Materials and Methods: CD133-positive Tu212 laryngeal carcinoma stem cells were purified by magnetic-activated cell sorting and subjected to hypoxic and/or low-glucose conditions. Proliferation was evaluated using a cell-counting kit and a clone-formation assay, and migration capability was measured through a Transwell assay. Autophagy was assessed using transmission electron microscopy. Gene silencing was monitored using shRNA technology and autophagy regulation was manipulated using rapamycin, 3-MA, or chloroquine. Gene expression levels were evaluated by quantitative reverse transcription-polymerase chain reaction and protein levels were assessed via Western blotting.Results: Compared to CD133-negative cells, CD133-positive cells showed increased proliferation and migration capabilities, and reduced apoptosis, under hypoxic or low-glucose conditions. CD133-positive cells also showed increased expression of GLUT-1 and autophagy activity. Finally, GLUT-1 knockdown or autophagy inhibition reduced the proliferation and migration of CD133-positive laryngeal carcinoma stem cells.Conclusion: Enhanced glucose uptake and autophagy maintain the tumor behaviors of CD133-positive laryngeal carcinoma stem cells under hypoxic and low-glucose conditions.Keywords: Laryngeal carcinoma, cancer stem cell, CD133-positive cell, GLUT-1, autophagy
