The effect of prolyl hydroxylase 3 (PHD3) in radioresistancy of head and neck
squamous cell carcinoma

Metsälä Olli

Heath biosciences, Drug Development

Miikkulainen Petra, Turku Centre for Biotechnology

Högel Heidi, Turku Centre for Biotechnology

Grönroos Tove, Turku PET Centre

Jaakkola Panu, Turku University Hospital

Head and neck squamous cell carcinomas (HNSCC) are sixth most common cancer
type in the world. HNSCC tumours typically tend to be poorly oxygenated,
especially in advanced cancers. Poor oxygenation, i.e. hypoxia, is caused by
disturbances in blood flow and dysfunctional structures of the intratumoral
vasculature. Hypoxia in cancer is associated with poor response to treatment
resulting from inadequate transportation of chemotherapeutics and ineffective
radiotherapy due to lack of oxygen. Therefore hypoxia makes the HNSCC harder to
cure, which raises the already high burden due to its prevalence.

Cellular response to hypoxia is primarily mediated by hypoxia inducible factor
(HIF), which is regulated by prolyl hydroxylase domain proteins (PHDs). PHDs
function by hydroxylating their target proteins, which leads to degradation of the
target (e.g. HIF) or it may lead to functional activation of the target. PHD3 isoform
is associated with nervous system development, but also with many pathological
conditions including cancer. PHD3 has been shown to regulate cellular
metabolism, cell-cycle checkpoint control, and to interact with proteins involved in
DNA damage repair.

In this study the effect of PHD3 in radioresistancy of HNSCC was studied with
PHD3 depleted and irradiated cells. The results show that PHD3 protects the
HNSCC cells from the effects of radiation and implicates a role for PHD3 in
radioresistancy of HNSCC cells.

Keywords: cancer, hypoxia, HNSCC, PHD3, radiation biology, radioresistancy