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

Abstract

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.

Prognostic and clinicopathological significance of CTTN/cortactin alterations in head and neck squamous cell carcinoma: Systematic review and meta‐analysis

“…The main mechanism of cortactin overexpression is the amplification of its gene, CTTN , located in chromosome band 11q13 . The amplification of 11q13 and the oncogenes in this region is a frequent event in HNSCC and exerts a major influence on its onset and progression .…”

“…Currently, research is focused on the prognostic value of emerging molecular biomarkers that may serve as a complement in clinical practice . Accumulated evidence suggests that CTTN /cortactin alterations play a key role in head and neck oncogenesis, particularly in the development of lymph node metastasis …”

“…Cortactin is a protein encoded by the CTTN gene in chromosome band 11q13 . CTTN is often amplified due to the frequent amplification of this chromosomal locus, promoting the overexpression of its product, cortactin, which is an important event in head and neck carcinogenesis .…”

“…CTTN is often amplified due to the frequent amplification of this chromosomal locus, promoting the overexpression of its product, cortactin, which is an important event in head and neck carcinogenesis . Cortactin downregulation appears to be associated with characteristically invasive cancers such as melanoma and it has been most widely investigated in the setting of head and neck cancers . Its name, cortactin, derives from its vicinity to cytoskeletal structures of cortical actin .…”

“…In addition, the interactions of cortactin with numerous proteins, notably Src and the Arp2/3 complex, give it an important role in the regulation of various cell events that are also related to regulation of the aforementioned protrusive structures . CTTN /cortactin alterations (amplification and overexpression) contribute to a gain in cell migration and invasiveness and have been extensively studied in vitro and in vivo in HNSCC . Since the first reports, numerous authors have addressed the relationship of CTTN /cortactin alterations with the development of lymph node metastasis and reduced survival in HNSCC .…”