The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis.
The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis.
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DOI：
10.3389/fendo.2017.00187
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发表时间：
2017
影响因子：
5.2
通讯作者：
Emons G
中科院分区：
文献类型：
--
作者：
Gründker C;Emons G
在几种人类泌尿生殖道恶性肿瘤中，包括子宫内膜癌、卵巢癌、膀胱癌和前列腺癌，已经可以鉴定出促性腺激素释放激素（GnRH）及其受体的表达，作为自分泌系统的一部分，调节细胞增殖。 GnRH 受体的表达也在乳腺癌和非生殖性癌症（如胰腺癌和胶质母细胞瘤）中被发现。各种研究人员观察到 GnRH 激动剂在这些癌症衍生的细胞系中具有剂量和时间依赖性的生长抑制作用。 GnRH 拮抗剂还对大多数癌细胞系显示出显着的生长抑制作用。这表明在癌细胞的GnRH系统中，GnRH激动剂和拮抗剂之间可能不存在二分法。 GnRH 受体存在于垂体促性腺激素中，众所周知的信号传导机制并不参与 GnRH 类似物在癌细胞中的抗增殖作用。相反，GnRH 受体激活磷酸酪氨酸磷酸酶 (PTP) 并抵消生长因子受体的有丝分裂信号转导，从而导致癌细胞增殖减少。由 GnRH 诱导的 PTP 激活也会抑制 G 蛋白偶联雌激素受体 1 (GPER)，这是雌激素的膜结合受体。 GPER 在不表达雌激素受体 α (ERα) 的乳腺癌中发挥着重要作用。在转移性乳腺癌、卵巢癌和子宫内膜癌细胞中，GnRH 可减少体外细胞侵袭、体内转移以及 S100A4 和 CYR61 表达的增加。所有这些因素在上皮间质转化中都发挥着重要作用。这篇综述将总结目前关于 GnRH 受体及其在人类癌症中信号传导的知识现状。
In several human malignant tumors of the urogenital tract, including cancers of the endometrium, ovary, urinary bladder, and prostate, it has been possible to identify expression of gonadotropin-releasing hormone (GnRH) and its receptor as part of an autocrine system, which regulates cell proliferation. The expression of GnRH receptor has also been identified in breast cancers and non-reproductive cancers such as pancreatic cancers and glioblastoma. Various investigators have observed dose- and time-dependent growth inhibitory effects of GnRH agonists in cell lines derived from these cancers. GnRH antagonists have also shown marked growth inhibitory effects on most cancer cell lines. This indicates that in the GnRH system in cancer cells, there may not be a dichotomy between GnRH agonists and antagonists. The well-known signaling mechanisms of the GnRH receptor, which are present in pituitary gonadotrophs, are not involved in forwarding the antiproliferative effects of GnRH analogs in cancer cells. Instead, the GnRH receptor activates a phosphotyrosine phosphatase (PTP) and counteracts with the mitogenic signal transduction of growth factor receptors, which results in a reduction of cancer cell proliferation. The PTP activation, which is induced by GnRH, also inhibits G-protein-coupled estrogen receptor 1 (GPER), which is a membrane-bound receptor for estrogens. GPER plays an important role in breast cancers, which do not express the estrogen receptor α (ERα). In metastatic breast, ovarian, and endometrial cancer cells, GnRH reduces cell invasion in vitro, metastasis in vivo, and the increased expression of S100A4 and CYR61. All of these factors play important roles in epithelial–mesenchymal transition. This review will summarize the present state of knowledge about the GnRH receptor and its signaling in human cancers.
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影响因子：
4.1
作者：
Dobkin-Bekman, Masha;Naidich, Michal;Naor, Zvi
通讯作者：
Naor, Zvi
影响因子：
11.2
作者：
Fister, Stefanie;Guenthert, Andreas R.;Gruendker, Carsten
通讯作者：
Gruendker, Carsten
DOI：
10.1097/igc.0000000000000044
发表时间：
2014-02
期刊：
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
影响因子：
--
作者：
Emons G;Gorchev G;Harter P;Wimberger P;Stähle A;Hanker L;Hilpert F;Beckmann MW;Dall P;Gründker C;Sindermann H;Sehouli J
通讯作者：
Sehouli J
影响因子：
5.8
作者：
EIDNE, KA;FLANAGAN, CA;MILLAR, RP
通讯作者：
MILLAR, RP
影响因子：
5.8
作者：
Eicke, N;Günthert, AR;Gründker, C
通讯作者：
Gründker, C