title: Human papillomavirus 16 E6 contributes HIF-1α induced Warburg effect by attenuating the VHL-HIF-1α interaction.
abstract: 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.
authors.affiliation: Department of gynecology, First Affiliated Hospital of China Medical University, Shenyang 110001, China. guoyi12@hotmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of gynecology, First Affiliated Hospital of China Medical University, Shenyang 110001, China. xiangkaimeng@hotmail.com.
authors.forename: Xiangkai
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Pain Management, Shengjing Hospital of China Medical University, Shenyang 110022, China. mming517@126.com.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of gynecology, First Affiliated Hospital of China Medical University, Shenyang 110001, China. Yahong516@163.com.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, First Affiliated Hospital of China Medical University, Shenyang 110001, China. qianwangyj@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, First Affiliated Hospital of China Medical University, Shenyang 110001, China. wangyn@163.com.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of AIDS Immunology of Ministry of Health, Department of Laboratory Medicine, First Affiliated Hospital of China Medical University, Shenyang 110001, China. shanghongyj@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
mesh_terms: D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D057809:HEK293 Cells; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications*; D012097:Repressor Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D005947:Glucose