Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma

Abstract

An understanding of the process by which tumor cells destroy the basement membrane of the surface epithelium, invade, and metastasize is essential to the development of novel treatment of head and neck squamous cell carcinoma (HNSCC). In recent years, there has been increased interest in the role of epithelial-mesenchymal transition (EMT) in invasion. EMT is a process that describes the development of motile, mesenchymal-like cells from non-motile parent epithelial cells. There are 3 known types of EMT that mediate development, wound healing, and carcinogenesis. This review summarizes studies of known EMT biomarkers in the context of HNSCC progression. The biomarkers discussed come from a wide range of proteins, including cell-surface proteins (E-cadherin, N-cadherin, and Integrins), cytoskeletal proteins (α-Smooth Muscle Actin, Vimentin, and β-catenin), extracellular matrix proteins (Collagens, Fibronectin, and Laminin), and transcription factors (SNAIL1, SNAIL2, TWIST, and LEF-1). Overall, the findings of these studies suggest that EMT mediates HNSCC progression. The mechanistic role of the EMT markers that have been associated with HNSCC should be more clearly defined if new anti-HNSCC therapies to block EMT progression are to be developed.KEY WORDS: disease progression, extracellular matrix, oral pathology, neoplasm invasiveness, biological markers, head and neck neoplasms.

Biomarkers for EMT and MET in breast cancer: An update

“…Vimentin is expressed at sites of cellular elongation, and is associated with a migratory phenotype. Increased vimentin expression is frequently used as an EMT marker in cancer (44,45). There is a positive correlation of vimentin expression with augmented invasiveness and metastasis.…”

Epithelial-mesenchymal axis in head and neck cancer cell lines

“…[9,32] This is a dynamic state where cells gain and maintain both epithelial and mesenchymal cell types. [32,33] When the HPV-16 positive cell lines are compared to each other at a protein level, UD-SCC2 has a more mesenchymal nature to it than 93-VU-147T due to lower expression of E-cadherin and no EpCAM expression and the presence of Vimentin which is frequently used as a marker of EMT. [33] Similar expression levels of E-cadherin and N-cadherin across the 7 cell lines.…”

“…[32,33] When the HPV-16 positive cell lines are compared to each other at a protein level, UD-SCC2 has a more mesenchymal nature to it than 93-VU-147T due to lower expression of E-cadherin and no EpCAM expression and the presence of Vimentin which is frequently used as a marker of EMT. [33] Similar expression levels of E-cadherin and N-cadherin across the 7 cell lines. In RPMI2650, there was a lack of expression of either of these two markers.…”

“…E-cadherins are calcium binding transmembrane glycoproteins involved in adhesion between epithelial cells by homophillic interactions. [33] E-cadherin expression has been found to be similarly expressed in primary and metastatic sites and this has been attributed to the reverse of EMT which the cells undergo, a process termed mesenchymal-epithelial transition (MET) at the metastatic sites. [33] Cadherin switching between E-cadherin and Ncadherin (e.g.…”

“…[33] E-cadherin expression has been found to be similarly expressed in primary and metastatic sites and this has been attributed to the reverse of EMT which the cells undergo, a process termed mesenchymal-epithelial transition (MET) at the metastatic sites. [33] Cadherin switching between E-cadherin and Ncadherin (e.g. Low expression of E-cadherin and high expression of N-cadherin) has been observed with an increase in invasion and metastasis.…”