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Szabo, R.* ; Ward, J.M.* ; Artunc, F. ; Bugge, T.H.*

EPCAM and TROP2 share role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice.

Biol. Open 11:bio059403 (2022)

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EPCAM (Epithelial Cell Adhesion Molecule) is a transmembrane glycoprotein expressed on the surface of most epithelial and epithelium-derived tumor cells and reported to regulate stability of epithelial tight junction proteins, claudins. Despite its widespread expression, loss of EPCAM function has so far only been reported to prominently affect intestinal development, resulting in severe early onset enteropathy associated with impaired growth and decreased survival in both humans and mice. In this study, we show that the critical role of EPCAM is not limited to intestinal tissues and that it shares its essential function with its only known homolog, TROP2 (Trophoblast cell surface antigen 2). EPCAM-deficient mice show significant growth retardation and die within four weeks after birth. In addition to changes in small and large intestines, loss of EPCAM results in hyperkeratosis in skin and forestomach, hair follicle atrophy leading to alopecia, nephron hypoplasia in kidney, proteinuria, and altered production of digestive enzymes by pancreas. Expression of TROP2 partially, but not completely, overlaps with EPCAM in a number developing epithelia. Although loss of TROP2 had no gross impact on mouse development and survival, TROP2 deficiency generally compounded developmental defects observed in EPCAM-deficient mice, led to about 60% decrease in embryonic viability, and further shortened postnatal lifespan of born pups. Importantly, TROP2 was able to compensate for the loss of EPCAM in stabilizing claudin-7 expression and cell membrane localization in tissues that co-express both proteins. These findings identify overlapping functions of EPCAM and TROP2 as regulators of epithelial development in both intestinal and extraintestinal tissues.

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Publication type Article: Journal article

Document type Scientific Article

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Keywords Claudin Stabilization ; Enteropathy ; Epithelial Development ; Hyperkeratosis ; Proteinuria

e-ISSN 2046-6390

Journal Biology Open

Quellenangaben Volume: 11, Issue: 7, Article Number: bio059403

Publisher Company of Biologists

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)

Grants Deutsche Forschungsgemeinschaft
Office of Extramural Research, National Institutes of Health