Loss of CPAP expression promotes sustained EGFR signaling and Epithelial-Mesenchymal Transition in oral cancer cells

Abstract

AbstractOral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC). Altered epidermal growth factor receptor (EGFR) levels can contribute to tumor metastasis and resistance to therapies. The epithelial-mesenchymal transition (EMT), by which epithelial cells acquire a mesenchymal and invasive phenotype, contributes significantly to tumor metastasis in OSCC, and EGFR signaling is known to promote this process. Microtubule inhibition therapies cause EGFR inactivation or increase the sensitivity to EGFR targeting drugs in various cancers including OSCC. In this study, using OSCC model, we show that loss of a microtubule/tubulin binding protein, centrosomal protein 4.1-associated protein (CPAP), which is critical for centriole biogenesis and normal functioning of centrosome, caused an increase in the EGFR levels and signaling and, enhanced the EMT features and invasiveness of OSCC cells. Further, depletion of CPAP increased the tumorigenicity of these cells in a xeno-transplant model. Importantly, CPAP loss-associated EMT features and invasiveness of multiple OSCC cells were attenuated upon depletion of EGFR in them. Overall, our novel observations suggest that in addition to its previously known regulatory role in centrosome biogenesis and function, CPAP plays an important role in suppressing EMT and tumorigenesis in OSCC by regulating EGFR homeostasis and signaling.