Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.237107v1?rss=1 Authors: Gudi, R., Janakiraman, H., Majumdar, M., Palanisamy, V., Howe, P., Vasu, C. Abstract: Oral 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 cellular levels of a microtubule/tubulin binding protein, centrosomal protein 4.1-associated protein (CPAP), which is critical for centriole biogenesis and normal functioning of centrosome, is upregulated upon treatment of OSCC cell lines with EGF. However, we found that loss of CPAP caused an increase in the EGFR levels and signaling and, enhanced the EMT features and invasiveness of OSCC cells. Further, loss 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. Copy rights belong to original authors. Visit the link for more info