Tumor Biology

, Volume 37, Issue 4, pp 4655–4663 | Cite as

Overexpression of HPV16 E6/E7 mediated HIF-1α upregulation of GLUT1 expression in lung cancer cells

  • Rong Fan
  • Wei-Jian Hou
  • Yu-Jie Zhao
  • Shu-Li Liu
  • Xue-Shan Qiu
  • En-Hua Wang
  • Guang-Ping Wu
Original Article


High-risk human papillomavirus (HPV) infection may play an important role in non-small cell lung carcinoma (NSCLC) development. However, some recent studies have proved that it was not directly associated with lung cancer. The aim of this study was to evaluate the underlying molecular mechanism that HPV16 regulate the expression of GLUT1 and may promote the development of lung cancer. HPV16, HIF-1α, and GLUT1 were detected in pleural effusions of patients with lung cancer (n = 95) and with benign lung disease (n = 55) by immunocytochemistry. Western blotting and qRT-PCR were used to detect the expression chances of HPV16 E6/E7, HIF-1α, and GLUT1 in lung cancer cells. HPV16, HIF-1α, and GLUT1 were significantly more likely to be expressed in the malignant group than in the benign group as detected by immunocytochemistry (ICC), and HIF-1α was significantly correlated with HPV16 or GLUT1 in the malignant group (P < 0.01). Expression changes of E6 and E7 significantly promoted the protein expression of HIF-1α, the expression of both protein and mRNA of GLUT1, but had no effect on the expression of HIF-1α mRNA in lung cancer cells. After inhibition of HIF-1α, it obviously downregulated the expression of both protein and mRNA of GLUT1 in lung cancer cells. E6 and E7 regulated the expression of GLUT1 may be due to the mediation of HIF-1α in lung cancer cells. These results suggest that both E6 and E7 play the important role in the regulation of Warburg effect and may be a valuable therapeutic target for HPV-related cancer.


Human papillomavirus (HPV) Lung cancer Hypoxia-inducible factor 1 Glucose transporter 1 Cytopathology 



Human papillomaviruses


Quantitative real-time reverse transcriptase-polymerase chain reaction


Hypoxia-inducible factor 1α


Glucose transporter 1


Non-small cell lung carcinoma


Human telomerase reverse transcriptase



This work was supported by grants from the National Natural Science Foundation of China to Guang-Ping Wu, Grant No. 81171650.

Compliance with ethical standards

The study was conducted according to the guidelines of the institutional review boards at the First Affiliated Hospital of China Medical University; we have obtained internal review board approval and/or patients’ informed consent for this study.

Conflicts of interest


Supplementary material

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Fig. S1A–B

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Rong Fan
    • 1
  • Wei-Jian Hou
    • 2
  • Yu-Jie Zhao
    • 3
  • Shu-Li Liu
    • 1
  • Xue-Shan Qiu
    • 1
  • En-Hua Wang
    • 1
  • Guang-Ping Wu
    • 1
  1. 1.Department of Pathology, The First Affiliated Hospital and College of Basic Medical SciencesChina Medical UniversityShenyangChina
  2. 2.Department of Tissue Engineering, College of Basic Medical SciencesChina Medical UniversityShenyangChina
  3. 3.Center of Biochip, College of Basic Medical SciencesChina Medical UniversityShenyangChina

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