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The role of polarity in early cancer

Sep. 21, 2021, 8:00 AM

by Shivani Sharma

Loss of polarity, the orientation of apical and basolateral surfaces of the epithelial cells that line most internal organs and body cavities, usually occurs early in cancer and is considered a consequence of malignant transformation.

Epidermal growth factor receptor (EGFR) is a major player in epithelial homeostasis and is often dysregulated in epithelial cancers. EGFR and its ligands predominantly localize to the basolateral cell surface.

Previously Bhuminder Singh, PhD, Robert Coffey, MD, and colleagues have shown that the apical mistrafficking of the EGFR ligand, epiregulin (EREG), is associated with in vivo transformation.

Reporting last month in the Journal of Cell Science, they show that expression of mutant EREG is sufficient to rapidly disrupt selected aspects of epithelial polarity.

Under normal conditions, most epithelia line a single central lumen, a phenotype that is recapitulated in three-dimensional in vitro cultures. 

Here, EREG mutations not only led to apical mistrafficking of EREG, but also induced global epithelial changes, namely emergence of multiple lumens instead of a single central lumen.

These findings suggest that loss of polarity of a single protein (EREG) may precipitate larger epithelial reorganization that might contribute to early cancer development.

Research support was provided through National Institutes of Health grants CA095103, CA197570 and TR002245, and the American Cancer Society.

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