Affiliation:
1. Key Laboratory of Pathobiology, Ministry of Education Norman Bethune College of Medicine, Jilin University Changchun Jilin Province China
2. Department of Urology The First Hospital of Jilin University Changchun China
3. Department of Medicine, School of Life Sciences Henan University Kaifeng Henan Province China
Abstract
AbstractOver 99% of precancerous cervical lesions are associated with human papillomavirus (HPV) infection, with HPV types 16 and 18 (especially type 16) found in over 70% of cervical cancer cases globally. E6, a critical HPV gene, triggers malignant proliferation by degrading p53; however, this mechanism alone cannot fully explain the oncogenic effects of HPV16 E6. Therefore, we aimed to investigate new targets of HPV oncogenic mechanisms. Our results revealed significant changes in nonoxidative pentose phosphate pathway (PPP) metabolites in HPV16‐positive cells. However, the role of nonoxidative PPP in HPV‐associated cell transformation and tumor development remained unexplored. In this study, we investigated the impact and mechanisms of HPV16 E6 on cervical cancer proliferation using the HPV‐negative cervical cancer cell line (C33A). HPV16 E6 was found to promote cervical cancer cell proliferation both in vitro and in vivo, activating the nonoxidative PPP. Transketolase (TKT), a key enzyme in the nonoxidative PPP, is highly expressed in cervical cancer tissues and associated with poor prognosis. HPV16 E6 promotes cervical cancer cell proliferation by upregulating TKT activity through the activation of AKT. In addition, oxythiamine (OT), a TKT inhibitor, hindered tumor growth, with enhanced effects when combined with cisplatin (DDP). In conclusion, HPV16 E6 promotes cervical cancer proliferation by upregulating TKT activity through the activation of AKT. OT demonstrates the potential to inhibit HPV16‐positive cervical cancer growth, and when combined with DDP, could further enhance the tumor‐suppressive effect of DDP.
Funder
National Natural Science Foundation of China
Subject
Cancer Research,Molecular Biology
Cited by
1 articles.
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