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

Abstract

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 bad response to treatment resulting from poor 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.

The cells 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 affects cellÕs metabolism, cell-cycle checkpoint control, and interacts 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 that PHD3 has a role in radioresistancy of HNSCC cells.