| Autor: |
Kuburich, Nick A., Kiselka, Julia M., den Hollander, Petra, Karam, Andrew A., Mani, Sendurai A. |
| Zdroj: |
Cancers; Dec2024, Vol. 16 Issue 24, p4158, 24p |
| Abstrakt: |
Simple Summary: Hybrid epithelial/mesenchymal (E/M) cells are the most metastatic of carcinoma cell types. Hybrid E/M cells have both epithelial and mesenchymal properties reminiscent of chimeras, mythical creatures composed of different animals. The co-expression of epithelial and mesenchymal proteins is a defining feature of hybrid E/M cancer cells. In this review, we discuss the use of cytokeratin (epithelial) and vimentin (mesenchymal) intermediate filaments as markers in hybrid E/M cells. We describe the structures and functions of these filaments that are uniquely expressed in hybrid E/M cells and speculate on potential hybrid structures formed between vimentin and cytokeratin. We also describe cell-surface cytokeratin and vimentin and their functions and discuss their potential as predictive biomarkers and as targets for anti-cancer therapy. The epithelial–mesenchymal transition (EMT) program is critical to metastatic cancer progression. EMT results in the expression of mesenchymal proteins and enhances migratory and invasive capabilities. In a small percentage of cells, EMT results in the expression of stemness-associated genes that provide a metastatic advantage. Although EMT had been viewed as a binary event, it has recently become clear that the program leads to a spectrum of phenotypes, including hybrid epithelial/mesenchymal (E/M) cells that have significantly greater metastatic capability than cells on the epithelial or mesenchymal ends of the spectrum. As hybrid E/M cells are rarely observed in physiological, non-diseased states in the adult human body, these cells are potential biomarkers and drug targets. Hybrid E/M cells are distinguished by the co-expression of epithelial and mesenchymal proteins, such as the intermediate filament proteins cytokeratin (CK; epithelial) and vimentin (VIM; mesenchymal). Although these intermediate filaments have been extensively used for pathological characterization and detection of aggressive carcinomas, little is known regarding the interactions between CK and VIM when co-expressed in hybrid E/M cells. This review describes the characteristics of hybrid E/M cells with a focus on the unique co-expression of VIM and CK. We will discuss the structures and functions of these two intermediate filament proteins and how they may interact when co-expressed in hybrid E/M cells. Additionally, we review what is known about cell-surface expression of these intermediate filament proteins and discuss their potential as predictive biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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