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Cited by 264PI3K/AKT/mTOR signaling in cancerCervical Cancer and HPV ResearchHead and Neck Cancer Studies

The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses

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Zhang, Lifang, Wu, Jianhong, Ling, Ming Tat, Zhao, Liang, Zhao, Kong-Nan·2015·Molecular Cancer
DOI 10.1186/s12943-015-0361-xPMC PMC4498560
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Abstract

Infection with Human papillomaviruses (HPVs) leads to the development of a wide-range of cancers, accounting for 5% of all human cancers. A prominent example is cervical cancer, one of the leading causes of cancer death in women worldwide. It has been well established that tumor development and progression induced by HPV infection is driven by the sustained expression of two oncogenes E6 and E7. The expression of E6 and E7 not only inhibits the tumor suppressors p53 and Rb, but also alters additional signalling pathways that may be equally important for transformation. Among these pathways, the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signalling cascade plays a very important role in HPV-induced carcinogenesis by acting through multiple cellular and molecular events. In this review, we summarize the frequent amplification of PI3K/Akt/mTOR signals in HPV-induced cancers and discuss how HPV oncogenes E6/E7/E5 activate the PI3K/Akt/mTOR signalling pathway to modulate tumor initiation and progression and affect patient outcome. Improvement of our understanding of the mechanism by which the PI3K/Akt/mTOR signalling pathway contributes to the immortalization and carcinogenesis of HPV-transduced cells will assist in devising novel strategies for preventing and treating HPV-induced cancers.

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  • Three oncoproteins, E5, E6, and E7, encoded by HPV, activated EGFR, MAPK, or PI3K/AKT/mTOR signaling cascades, resulting in the phosphorylation of BAD.

    “It has been reported that three oncoproteins, E5, E6, and E7, encoded by HPV, activated EGFR, MAPK, or PI3K/AKT/mTOR signaling cascades, resulting in the phosphorylation of BAD [29].”

    From Combining Mitomycin C with inhibition of BAD phosphorylation enhances apoptotic cell death in advanced cervical cancer (2024) · cites this paper as [29]

    The E5 and E6 oncogene sections describe activation of EGFR, MAPK, and PI3K/Akt-related signaling, while the E7 oncogene section explicitly links E7-driven Akt activation to BAD phosphorylation (page numbers unavailable). The paper does not establish that E5 or E6 signaling also results in BAD phosphorylation, as the citing sentence implies. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Zhang, L., Wu, J., Ling, M. T., Zhao, L., & Zhao, K.-N.
Affiliations
  • Wenzhou Medical University (CN)
  • Queensland University of Technology (AU)
  • The University of Queensland (AU)
  • Translational Research Institute (AU)
Corresponding author
Zhao, Kong-Nan
ORCID
Venue
Molecular Cancer
Publisher
Springer Science and Business Media LLC
Published
2015-04-17
Volume
14
Issue
1
Pages
87-87
ISSN
1476-4598 (ISSN-L)
DOI
10.1186/s12943-015-0361-x
PMC
PMC4498560
OpenAlex
W2098204011
Cited by
264
References
4
Citations by year
2026: 33 · 2025: 34 · 2024: 30 · 2023: 27 · 2022: 32 · 2021: 31 · 2020: 22 · 2019: 13 · 2018: 23 · 2017: 9 · 2016: 7 · 2015: 3
FWCI
1.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cancer (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (81172463)
  • Medical Research Council
  • National Health and Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Keywords
PI3K/AKT/mTOR pathway, human papillomavirus, HPV-induced carcinogenesis, cervical cancer, E6 oncoprotein, E7 oncoprotein, p53, retinoblastoma protein, cell immortalization, tumor progression, patient outcomes
MeSH terms
MAP-Kinase-Activated Kinase 2, Animals, Cell Transformation, Viral, Humans, Life Cycle Stages, Neoplasms, Signal Transduction, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Papillomaviridae, Papillomavirus Infections, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Ataxia Telangiectasia Mutated Proteins

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