GPR54 is a target for suppression of metastasis in endometrial cancer.
نویسندگان
چکیده
Invasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis, resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, kisspeptin (KISS1), and its endogenous receptor, GPR54, has been reported in several cancers, but the significance of the KISS1/GPR54 axis in endometrial cancer metastasis has not been clarified. Metastin-10 is the minimal bioactive sequence of genetic products of KISS1. Clinicopathological analysis of 92 endometrial cancers revealed overall survival is improved in cancers with high expression of GPR54 (P < 0.05) and that GPR54 expression is associated with known prognostic factors including FIGO stage, grade, and deep myometrial invasion. Through RNAi and microarray analyses, metastin-10 was predicted to suppress metastasis of GPR54-expressing endometrial cancers in vivo. Methylation analysis revealed GPR54 is epigenetically regulated. Metastin-GPR54 axis function was restored following treatment with the DNA hypomethylating agent 5-aza-DC. These data suggest that metastin-10 may be effective at inhibiting the metastatic spread of endometrial cancers in combination with demethylating agents to induce GPR54 expression.
منابع مشابه
Kisspeptins (KiSS-1): essential players in suppressing tumor metastasis.
Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP- 10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fer...
متن کاملBioinformatics-Based Prediction of FUT8 as a Therapeutic Target in Estrogen Receptor-Positive Breast Cancer
Abstract Introduction: Estrogen receptor-positive (ER-positive) breast cancer is a subgroup of breast tumors that is more likely to respond to hormone therapy. ER-positive and ER- negative breast cancers tend to show different patterns of metastasis because of different signaling cascade and genes that are activated by estrogen response. Genetic factors can contribute to high rates of metastas...
متن کاملBioinformatics-Based Prediction of FUT8 as a Therapeutic Target in Estrogen Receptor-Positive Breast Cancer
Abstract Introduction: Estrogen receptor-positive (ER-positive) breast cancer is a subgroup of breast tumors that is more likely to respond to hormone therapy. ER-positive and ER- negative breast cancers tend to show different patterns of metastasis because of different signaling cascade and genes that are activated by estrogen response. Genetic factors can contribute to high rates of metastas...
متن کاملA Mimic of the Tumor Microenvironment on GPR30 Gene Expression in Breast Cancer
Introduction: The G-protein coupled receptor 30 (GPR30) gene is a member of the G-protein coupled receptor (GPCR) family; involved in breast, endometrial, and ovarian cancers. Many GPCR receptors that are implicated in several types of human cancers are correlated with increased cell proliferation and tumor progression; especially GPR30 gene. Methods: The breast cancer MCF-7 and MDA-MB-231 cel...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Molecular cancer therapeutics
دوره 10 4 شماره
صفحات -
تاریخ انتشار 2011