DOI: 10.1101/507954Dec 29, 2018Paper

Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Akt - NF?B - IL-6 signalling axis

BioRxiv : the Preprint Server for Biology
Ethan Luc Morgan, Andrew Macdonald

Abstract

Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Although the fundamental link between HPV infection and oncogenesis is established, the specific mechanisms of virus-mediated transformation remain poorly understood. We previously demonstrated that the HPV encoded E6 protein increases the activity of the proto-oncogenic transcription factor STAT3 in primary human keratinocytes; however, the molecular basis for STAT3 activation in cervical cancer remains unclear. Here, we show that STAT3 phosphorylation in HPV positive cervical cancer cells is mediated primarily via autocrine activation by the pro-inflammatory cytokine Interleukin 6 (IL-6). Antibody-mediated blockade of IL-6 signalling in HPV positive cells inhibits STAT3 phosphorylation, whereas both recombinant IL-6 and conditioned media from HPV positive cells leads to increased STAT3 phosphorylation within HPV negative cervical cancer cells. Interestingly, we demonstrate that non-conventional activation of the transcription factor NF?B, involving the protein kinase Akt, is required for IL-6 production and subsequent STAT3 activation. Our data provides new insights into the molecular re-wiring of cancer cells by HPV E6. We reveal that ac...Continue Reading

Related Concepts

Human Papillomavirus
Interleukin-6
Keratinocyte
Papillomavirus
Phosphorylation
Protein KINASE
Signal Pathways
Transcription Factor
Transformation, Genetic
Virus

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