Unknown

Dataset Information

0

Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer.


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.

SUBMITTER: Lal-Nag M 

PROVIDER: S-EPMC3511677 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer.

Lal-Nag M M   Battis M M   Santin A D AD   Morin P J PJ  

Oncogenesis 20121112


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  ...[more]

Similar Datasets

| S-EPMC7488353 | biostudies-literature
| S-EPMC8431234 | biostudies-literature
| S-EPMC10077899 | biostudies-literature
| S-EPMC2795001 | biostudies-literature
| S-EPMC5768141 | biostudies-literature
| S-EPMC8618062 | biostudies-literature
| S-EPMC8533227 | biostudies-literature
| S-EPMC3137611 | biostudies-literature
| S-EPMC4004164 | biostudies-literature
| S-EPMC7068056 | biostudies-literature