title: The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses.
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.
authors.affiliation: Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, 325035 , Zhejiang, PR China. wenzhouzlf@126.com.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, 37 Kent Street, Woolloongabba, Brisbane, 4102, QLD, Australia. elite53@gmail.com.|Current address: Department of Gastric Cancer and Soft Tissue Sarcomas Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China. elite53@gmail.com.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, 37 Kent Street, Woolloongabba, Brisbane, 4102, QLD, Australia. mingtat.ling@qut.edu.au.
authors.forename: Ming Tat
authors.initials: MT
authors.lastname: Ling
authors.affiliation: The University of Queensland, Brisbane, 4072, QLD, Australia. l.zhao@imb.uq.edu.au.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, 325035 , Zhejiang, PR China. k.zhao@uq.edu.au.|Centre for Kidney Disease Research-Venomics Research, The University of Queensland School of Medicine, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, 4102, QLD, Australia. k.zhao@uq.edu.au.
authors.forename: Kong-Nan
authors.initials: KN
authors.lastname: Zhao
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002472:Cell Transformation, Viral; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008018:Life Cycle Stages; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism*; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2