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Human papillomavirus 16 E6 contributes HIF-1? induced Warburg effect by
attenuating the VHL-HIF-1? interaction
#MMPMID24810689
Guo Y
; Meng X
; Ma J
; Zheng Y
; Wang Q
; Wang Y
; Shang H
Int J Mol Sci
2014[May]; 15
(5
): 7974-86
PMID24810689
show ga
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
1? (HIF-1?), a ubiquitously expressed transcriptional regulator involved in
induction of numerous genes associated with angiogenesis and tumor growth, is
highly increased by HPV E6. HIF-1? 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-1? and VHL. This disassociation
attenuates VHL-mediated HIF-1? ubiquitination and causes HIF-1? 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.
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