An update of knowledge on cortactin as a metastatic driver and potential therapeutic target in oral squamous cell carcinoma

Cortactin is a protein encoded by the CTTN gene, localized on chromosome band 11q13. As a result of the amplification of this band, an important event in oral carcinogenesis, CTTN is also usually amplified, promoting the frequent overexpression of cortactin. Cortactin enhances cell migration in oral cancer, playing a key role in the regulation of filamentous actin and of protrusive structures (invadopodia and lamellipodia) on the cell membrane that are necessary for the acquisition of a migratory phenotype. We also analyze a series of emerging functions that cortactin may exert in oral cancer (cell proliferation, angiogenesis, regulation of exosomes, and interactions with the tumor microenvironment). We review its molecular structure, its most important interactions (with Src, Arp2/3 complex, and SH3‐binding partners), the regulation of its functions, and its specific oncogenic role in oral cancer. We explore the mechanisms of its overexpression in cancer, mainly related to genetic amplification. We analyze the prognostic implications of the oncogenic activation of cortactin in potentially malignant disorders and in head and neck cancer, where it appears to be relevant in the development of lymph node metastasis. Finally, we discuss its usefulness as a therapeutic target and suggest future research lines.