Human papillomavirus-16 E6 activates the pentose phosphate pathway to promote cervical cancer cell proliferation by inhibiting G6PD lactylation
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View abstract on PubMed
Summary
This summary is machine-generated.High-risk human papillomaviruses (HPVs) activate the pentose phosphate pathway (PPP) to promote cervical cancer. HPV16 E6 inhibits G6PD lactylation, enhancing PPP activity and cell proliferation, offering new therapeutic targets.
Area Of Science
- Oncology
- Virology
- Biochemistry
Background
- High-risk human papillomaviruses (HPVs) are primary causes of cervical cancer.
- Oncoproteins like HPV16 E6E7 play a crucial role in cancer development.
- The pentose phosphate pathway (PPP) is vital for cellular metabolism and redox balance.
Purpose Of The Study
- To investigate the mechanism by which HPV16 E6E7 promotes cervical cancer cell proliferation.
- To elucidate the role of the pentose phosphate pathway (PPP) in HPV-associated cervical cancer.
- To identify potential therapeutic targets for cervical cancer treatment.
Main Methods
- Investigated HPV16 E6E7's effect on PPP activation in cervical cancer cells.
- Assessed the impact of HPV16 E6 on glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and lactylation.
- Utilized genetic manipulation (G6PD K45A and K45T mutants) in cell lines and in vivo models.
- Administered 6-aminonicotinamide (6-An) to inhibit G6PD activity in vivo.
Main Results
- HPV16 E6E7 activates the PPP, driving cervical cancer cell proliferation.
- HPV16 E6 increases G6PD activity by inhibiting its lactylation at K45.
- Modulating G6PD lactylation affects cellular redox balance (GSH, NADPH, ROS) and proliferation.
- Inhibition of G6PD activity or mimicking constitutive lactylation suppressed tumor growth in vivo.
Conclusions
- HPV16 E6E7 hijacks the PPP via G6PD lactylation to promote cervical cancer.
- Targeting G6PD lactylation and PPP activity presents a novel therapeutic strategy for HPV-associated cancers.
- This study reveals a new mechanism of HPV-driven oncogenesis.
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