Human Papillomavirus 16 E6 Contributes HIF-1α Induced Warburg Effect by Attenuating the VHL-HIF-1α Interaction

International Journal of Molecular Sciences

Yi Guo¹  Xiangkai Meng¹  Jiaming Ma²  Yahong Zheng¹  Qian Wang³  Yanan Wang³ 

[1] Department of Gynecology, First Affiliated Hospital of China Medical University, Shenyang 110001, China; E-Mails:;Department of Pain Management, Shengjing Hospital of China Medical University, Shenyang 110022, China; E-Mail:;Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, First Affiliated Hospital of China Medical University, Shenyang 110001, China; E-Mails:

关键词: HPV16 E6;    hypoxia inducible factor-1 (HIF-1);    Warburg effect;    von Hippel-Lindau tumor suppressor gene (VHL);   

DOI  :  10.3390/ijms15057974

来源: mdpi

【 摘 要 】

Cervical cancer is still one of the leading causes of cancer deaths in women worldwide, especially in the developing countries. It is a major metabolic character of cancer cells to consume large quantities of glucose and derive more energy by glycolysis even in the presence of adequate oxygen, which is called Warburg effect that can be exaggerated by hypoxia. The high risk subtype HPV16 early oncoprotein E6 contributes host cell immortalization and transformation through interacting with a number of cellular factors. Hypoxia-inducible factor 1α (HIF-1α), a ubiquitously expressed transcriptional regulator involved in induction of numerous genes associated with angiogenesis and tumor growth, is highly increased by HPV E6. HIF-1α is a best-known target of the von Hippel-Lindau tumor suppressor (VHL) as an E3 ligase for degradation. In the present work, we found that HPV16 E6 promotes hypoxia induced Warburg effect through hindering the association of HIF-1α and VHL. This disassociation attenuates VHL-mediated HIF-1α ubiquitination and causes HIF-1α accumulation. These results suggest that oncoprotein E6 plays a major role in the regulation of Warburg effect and can be a valuable therapeutic target for HPV-related cancer.

【 授权许可】

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