Open AccessUrocortin suppresses endometrial cancer cell migration via CRFR2 and its system components are differentially modulated by estrogen
Author(s) -
Owens Gemma L.,
Lawrence Kevin M.,
Jackson Tom R.,
Crosbie Emma J.,
Sayan Berna S.,
Kitchener Henry C.,
Townsend Paul A.
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.967
Subject(s) - urocortin , endometrial cancer , receptor , cancer research , estrogen , estrogen receptor , medicine , carcinogenesis , chemistry , endocrinology , cell migration , biology , cell , cancer , breast cancer , biochemistry
Urocortin ( UCN 1) peptide shares structural and functional homology with corticotropin‐releasing factor ( CRF ). UCN 1 is significantly reduced in endometrial adenocarcinoma compared to healthy controls. However, there are no data which evaluate the effects of UCN 1 in the endometrium, or how it is modulated. We used proliferation and transwell assays to determine the effect of UCN 1 on the proliferation and migration of Ishikawa and HEC 1A cells. We also determined the expression levels of UCN 1 and its receptors produced by estrogen receptor agonists, and the effect of UCN 1 on estrogen receptor expression, using quantitative polymerase chain reaction. UCN 1 suppressed migration of endometrial cancer cells in vitro. This effect appears to be specific to CRF receptor 2 ( CRFR 2), as selective antagonism of CRFR 2 but not CRFR 1 completely eliminated suppression of migration. Activation of ERA reduced UCN 1 expression, but only had a small effect on the expression of CRFR 1. However, expression of CRFR 2 was more notably reduced at both the m RNA and protein levels by activation of ERB . UCN 1 in turn reduced both ERA and ERB expression, as assessed by real‐time quantitative PCR . We demonstrate that UCN 1 significantly suppresses the migration of endometrial cancer cells but has no effect on their proliferation. Thus, loss of UCN 1 in endometrial cancer may promote invasion and metastatic spread. There is a complex relationship between the UCN 1 system and estrogen receptors, which may provide insights into endometrial carcinogenesis, a disease known to be driven by estrogen excess.