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

Molecular Cancer

Review

Ming Tat Ling¹  Jianhong Wu²  Lifang Zhang³  Kong-Nan Zhao⁴  Liang Zhao⁵ 

[1] Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, 37 Kent Street, Woolloongabba, 4102, Brisbane, QLD, Australia;Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, 37 Kent Street, Woolloongabba, 4102, Brisbane, QLD, Australia;Current address: Department of Gastric Cancer and Soft Tissue Sarcomas Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, PR China;Institute of Molecular Virology and Immunology, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, PR China;Institute of Molecular Virology and Immunology, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, PR China;Centre for Kidney Disease Research-Venomics Research, The University of Queensland School of Medicine, Translational Research Institute, 37 Kent Street, Woolloongabba, 4102, Brisbane, QLD, Australia;The University of Queensland, 4072, Brisbane, QLD, Australia;

关键词: Cancer;    Human papillomavirus;    E6;    E7;    E5;    Phosphatidylinositol 3-kinase (PI3K);    Akt;    Mammalian target of rapamycin (mTOR);   

DOI  :  10.1186/s12943-015-0361-x

 received in 2014-11-20, accepted in 2015-04-06,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Zhang et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.