Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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Four Major Factors Regulate Phosphatidylinositol 3-kinase Signaling Pathway in Cancers Induced by Infection of Human Papillomaviruses

Author(s): Jianghong Wu, Jiezhong Chen, Lifang Zhang, Paul P. Masci, Kong-Nan Zhao.

Abstract:

Epidemiological surveys and molecular studies have indicated that infection of human papillomavirus (HPV)itself is necessary but insufficient for completing transformation of the human epithelial cells in vivo to lead to different cancers. Mounting evidence exists that HPV E6/E7 oncoproteins indeed alter the cellular and molecular events in their transformed cells to induce cancers through a phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. The PI3K/AKT/mTOR signaling pathway is, nonetheless, of the central importance, which tightly modulates many cellular events that occur in cells to lead them to be cancerous under the action of oncogenic factors. The cancinogenic roles of the PI3K/AKT/mTOR signaling in HPV-induced cancers are generally regulated by different upstream signaling molecules such as upstream receptor tyrosine kinases. In this article, we review that the four major upstream signaling molecules (growth factor receptor, notch receptor, Ras and PI3KCA genes) regulate PI3K/AKT/mTOR pathway to confer oncogenicity in HPV-immortalized epithelial cells and various transformed phenotypes.

Keywords: AKT, growth factor receptor, human papillomavirus, mammalian target of rapamycin (mTOR), notch receptor, phosphatidylinositol 3-kinase (PI3K), PI3KCAgene, rasgene.

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Article Details

VOLUME: 21
ISSUE: 26
Year: 2014
Page: [3057 - 3069]
Pages: 13
DOI: 10.2174/0929867321666140414101528
Price: $58