Public-private partnerships and the politics of alcohol policy in England : the Coalition Government's Public Health 'Responsibility Deal'

BACKGROUND: The 2010-2015 Conservative-led Coalition Government launched their flagship Public Health Responsibility Deal (PHRD) for England in 2011; a year before their alcohol strategy. This co-regulatory regime placed alcohol industry actors at the heart of policy-making, but was viewed with scepticism by public health actors. This article examines the ways in which the PHRD structured the alcohol policy environment throughout this period, which included the rejection of evidence-based policies such as minimum unit pricing. METHODS: This article draws on 26 semi-structured interviews with policy actors (parliamentarians, civil servants, civil society actors and academics) in 2018. Respondents were identified and recruited using purposive sampling. Interviews were recorded, transcribed and analysed using thematic coding. RESULTS: The PHRD shaped the context of alcohol policy development at Westminster throughout this period. It circumscribed the policy space by taking evidence-based measures not amenable to industry partnership off the agenda. While the PHRD created important opportunities for industry engagement with policy-makers, it undermined public health actors' access to government, particularly following their withdrawal from the process. Moreover, the PHRD demonstrates the enduring appeal of partnership as a policy idea for governments, despite a lack of evidence of their effectiveness. CONCLUSIONS: This study of the PHRD demonstrates the ways in which industry actors are able to influence policy through long-term relationship building and partnership working on policy decision-making. Whilst such partnership approaches may appear to have the potential to mitigate some of alcohol harms, they create fundamental conflicts of interest, and may undermine the very causes they seek to further

E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer

Human papillomaviruses (HPV) are a major cause of malignancy worldwide, contributing to ~5% of all human cancers including almost all cases of cervical cancer and a growing number of ano-genital and oral cancers. HPV-induced malignancy is primarily driven by the viral oncogenes, E6 and E7, which manipulate host cellular pathways to increase cell proliferation and enhance cell survival, ultimately predisposing infected cells to malignant transformation. Consequently, a more detailed understanding of viral-host interactions in HPV-associated disease offers the potential to identify novel therapeutic targets. Here, we identify that the c-Jun N-terminal kinase (JNK) signalling pathway is activated in cervical disease and in cervical cancer. The HPV E6 oncogene induces JNK1/2 phosphorylation in a manner that requires the E6 PDZ binding motif. We show that blockade of JNK1/2 signalling using small molecule inhibitors, or knockdown of the canonical JNK substrate c-Jun, reduces cell proliferation and induces apoptosis in cervical cancer cells. We further demonstrate that this phenotype is at least partially driven by JNK-dependent activation of EGFR signalling via increased expression of EGFR and the EGFR ligands EGF and HB-EGF. JNK/c-Jun signalling promoted the invasive potential of cervical cancer cells and was required for the expression of the epithelial to mesenchymal transition (EMT)-associated transcription factor Slug and the mesenchymal marker Vimentin. Furthermore, JNK/c-Jun signalling is required for the constitutive expression of HPV E6 and E7, which are essential for cervical cancer cell growth and survival. Together, these data demonstrate a positive feedback loop between the EGFR signalling pathway and HPV E6/E7 expression, identifying a regulatory mechanism in which HPV drives EGFR signalling to promote proliferation, survival and EMT. Thus, our study has identified a novel therapeutic target that may be beneficial for the treatment of cervical cancer