Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-11

AUTHORS

M Lal-Nag, M Battis, A D Santin, P J Morin

ABSTRACT

Claudins are integral tight junction proteins that are responsible for maintaining the integrity of epithelial cell architecture and cell polarity. Claudin-3 and -4 are overexpressed in several cancers and have been shown to act as receptors for the Clostridium perfringens enterotoxin (CPE), a toxin that causes rapid cell lysis. CPE has demonstrated effectiveness in treating several different cancers in mouse models, provided that these cancers express claudin-3 or claudin-4. Here, we show that claudin-3/4 expression is not an absolute requirement for CPE action and, through overexpression and knockdown experiments, we identify claudin-6 as a novel functional receptor for CPE. Indeed, UCI-101, an ovarian cancer cell line highly sensitive to CPE, does not express claudin-3/4 and knockdown of claudin-6 in these cells decreases CPE sensitivity. Moreover, two different ovarian cell lines that are resistant to the effects of CPE can be made sensitive through claudin-6 overexpression. Binding assays show that CPE can indeed bind claudin-6 in cells and that this binding is associated with CPE cytotoxicity. Multicellular tumor spheroids experiments demonstrate that claudin-6 can also be a target of CPE in three-dimensional cultures. Our data establish claudin-6 as a novel receptor for CPE and introduces the possibility of a novel targeted therapeutic for ovarian and other cancers that express claudin-6. More... »

PAGES

e33

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/oncsis.2012.32

DOI

http://dx.doi.org/10.1038/oncsis.2012.32

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047575767

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23552466


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