EPLIN as a Molecular Target of Genistein in Preventing Prostate Cancer Metastasis

EPLIN 作为金雀异黄素预防前列腺癌转移的分子靶点

基本信息

批准号：
8854250
负责人：
DAQING WU
金额：
$ 10.38万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-09 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8854250
关键词：
EPLIN Molecular Target Genistein Preventing

项目摘要

DESCRIPTION (provided by applicant): EPLIN as a Molecular Target of Genistein In Preventing Prostate Cancer Metastasis Genistein, a major dietary isoflavone whose consumption is associated with decreased rate of metastasis and reduced risk of mortality in patients, has emerged as a promising inhibitor of PCa metastasis. Nonetheless, the mechanism of action of genistein in blocking metastatic cascade in cancer cells remains largely unknown. In this application, we will test the hypothesis that the induction of EPLIN is a major mechanism wherein genistein inhibits the acquisition of invasiveness by PCa cells and prevents tumor metastasis. We proposed two Specific Aims. In Aim 1, we will elucidate the molecular mechanism by which genistein upregulates EPLIN and inhibits EMT in PCa cells. The hypothesis is that genistein induces EPLIN expression at transcriptional level, thereby inhibiting EMT and suppressing invasive phenotypes in PCa cells. We will determine whether genistein activates EPLIN promoter by inhibiting Snail-dependent repression of EPLIN promoter. The in vitro effects of genistein on EMT and invasiveness of PCa cells will be examined. This Aim will elucidate a novel mechanism of action of genistein in blocking the metastatic cascade in PCa cells. In Aim 2, we will determine the in vivo effects of genistein in upregulating EPLIN and preventing metastasis in pre-clinical PCa models. The hypothesis is that in vivo administration of genistein could effectively increase EPLIN expression and significantly reduce metastatic incidence in animal models. Two experimental models for PCa metastasis, i.e., TRAMP mice and orthotopic inoculation of PCa cells in SCID mice, will be used to evaluate the in vivo efficacy of genistein in upregulating EPLIN, inhibiting EMT and reducing metastatic incidence. These studies will validate EPLIN as a major molecular target of genistein, which could be exploited clinically for preventing PCa metastasis.

描述（由申请人提供）：EPLIN 作为金雀异黄酮的分子靶点预防前列腺癌转移金雀异黄酮是一种主要的膳食异黄酮，其摄入量与降低患者转移率和降低死亡率风险相关，已成为一种有前途的 PCa 抑制剂转移。尽管如此，金雀异黄素阻断癌细胞转移级联的作用机制仍然很大程度上未知。在本申请中，我们将测试以下假设：EPLIN 的诱导是金雀异黄素抑制 PCa 细胞获得侵袭性并防止肿瘤转移的主要机制。我们提出了两个具体目标。在目标 1 中，我们将阐明金雀异黄素上调 EPLIN 并抑制 PCa 细胞 EMT 的分子机制。假设金雀异黄素在转录水平诱导 EPLIN 表达，从而抑制 PCa 细胞中的 EMT 并抑制侵袭表型。我们将确定金雀异黄素是否通过抑制 EPLIN 启动子的 Snail 依赖性抑制来激活 EPLIN 启动子。将检查金雀异黄素对 PCa 细胞 EMT 和侵袭性的体外影响。该目标将阐明金雀异黄素阻断 PCa 细胞转移级联的新作用机制。在目标 2 中，我们将确定金雀异黄素在临床前 PCa 模型中上调 EPLIN 和预防转移的体内作用。假设在动物模型中体内施用金雀异黄素可以有效增加 EPLIN 表达并显着降低转移发生率。两个PCa转移实验模型，即TRAMP小鼠和SCID小鼠PCa细胞原位接种，将用于评估金雀异黄素上调EPLIN、抑制EMT和降低转移发生率的体内功效。这些研究将验证 EPLIN 是金雀异黄素的主要分子靶标，可在临床上用于预防 PCa 转移。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Epithelial protein lost in neoplasm (EPLIN): Beyond a tumor suppressor.

肿瘤中丢失的上皮蛋白 (EPLIN)：超越肿瘤抑制因子。

DOI：
发表时间：
2017-06
期刊：
影响因子：
6.8
作者：
Wu; Daqing
通讯作者：
Daqing

Mifepristone Has Limited Activity to Enhance the In Vivo Efficacy of Docetaxel and Enzalutamide Against Bone Metastatic and Castration-Resistant Prostate Cancer.

米非司酮增强多西他赛和恩杂鲁胺对抗骨转移性和去势抵抗性前列腺癌的体内疗效的活性有限。

DOI：
10.21873/anticanres.12074
发表时间：
2017-11-01
期刊：
Anticancer research
影响因子：
2
作者：
Yang Yang;Xin Li;K. Mamouni;O. Kucuk;Daqing Wu
通讯作者：
Daqing Wu

Pomegranate extract inhibits the bone metastatic growth of human prostate cancer cells and enhances the in vivo efficacy of docetaxel chemotherapy.

石榴提取物抑制人前列腺癌细胞的骨转移生长，增强多西紫杉醇化疗的体内疗效。

DOI：
发表时间：
2013-12-23
期刊：
影响因子：
0
作者：
Wang, Yanru;Zhang, Shumin;Iqbal, Shareen;Chen, Zhengjia;Wang, Xiaojing;Wang, Yongqiang A;Liu, David;Bai, Kevin;Ritenour, Chad;Kucuk, Omer;Wu, Daqing
通讯作者：
Wu, Daqing

Small molecule BKM1972 inhibits human prostate cancer growth and overcomes docetaxel resistance in intraosseous models.

小分子 BKM1972 在骨内模型中抑制人前列腺癌生长并克服多西紫杉醇耐药性。

DOI：
10.1016/j.canlet.2019.01.010
发表时间：
2019-04-01
期刊：
Cancer letters
影响因子：
9.7
作者：
Yanhua Chen;L. Gera;Shumin M. Zhang;Xin Li;Yang Yang;K. Mamouni;A. Wu;Hongyan Liu;O. Kucuk;Daqing Wu
通讯作者：
Daqing Wu

Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells.

金雀异黄素增强卡巴他赛化疗对转移性去势抵抗性前列腺癌细胞的疗效。

DOI：
发表时间：
2013-11
期刊：
影响因子：
0
作者：
Zhang, Shumin;Wang, Yanru;Chen, Zhengjia;Kim, Sungjin;Iqbal, Shareen;Chi, Andrew;Ritenour, Chad;Wang, Yongqiang A;Kucuk, Omer;Wu, Daqing
通讯作者：
Wu, Daqing