The TAZ transcriptional co-activator as a type specific arbiter of HPV driven cervical cancer

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Despite excellent vaccines, long term infection with so-called 'high-risk' human papillomaviruses (HPV) is the cause of 5% of the global cancer burden (~600,000 cancers per year). These cancers include nearly all cervical cancers, other cancers of the ano-genital tract (anal, vaginal, penile) and a growing number of oral cancers. These cancers predominantly impact on low and middle income countries, where the death rate can be 18 times higher than in developed countries. Limited vaccine availability in low income countries, vaccine hesitancy in developed countries and the lag between infection and disease ensures that the burden of HPV-associated disease remains high. As such, HPV still represents a major burden in many clinical settings and new therapies are desperately needed to complement the existing vaccines.HPVs must re-wire the cells they infect to create an environment in which they can reproduce and establish a long-term infection. As a parasite, the virus needs to take over the host cell machinery for this to happen. Understanding which host cell factors are vital for the virus to reproduce and to cause disease may help us to identify targets for new therapies.We have identified that the expression of the host protein TAZ is increased in HPV infected cells. TAZ controls gene expression and its expression and activity are often uncontrolled in cancers. Despite this, we do not fully understand how TAZ works, how it is regulated and which host genes it switches on or off. Our data shows that HPV needs TAZ to be switched in order for cervical cancer cells to grow. In this project we will aimTo understand how TAZ expression is increased, how TAZ functions in cervical cancer cells and which host gene products are important in cervical cancers. Our work will have impact in terms of helping us to understand which host factors are important for HPV-driven diseases and more broadly we will uncover new knowledge about how host proteins contribute to cancer.