FLT1 kinase is a mediator of radioresistance and survival in head and neck squamous cell carcinoma

AbstractHead and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide, responsible for approximately half a million new cases every year. The treatment of this disease is challenging and characterised by high rates of therapy failure and toxicity, stressing the need for new innovative treatment strategies. Material and methods. In this study we performed a shRNAmir-based screen on HNSCC cells with the aim to identify tyrosine kinases that are mediating radiotherapy resistance. Results. The receptor tyrosine kinase FLT1 (VEGFR1) was identified as an important driver of cell survival and radioresistance. We show that FLT1 is phosphorylated in HNSCC cells, and document autocrine production of FLT1 ligands VEGFA and VEGFB, leading to receptor activation. Immunohistochemistry on HNSCC patient samples demonstrated FLT1 and VEGFA to be uniformly expressed. Interestingly, FLT1 was selectively overexpressed in tumour tissue as compared to non-cancerous epithelium. Remarkably, we found...