Relaxin 2/RXFP1 Signaling Induces Cell Invasion via the β-Catenin Pathway in Endometrial Cancer.
Relaxin 2/RXFP1 Signaling Induces Cell Invasion via the β-Catenin Pathway in Endometrial Cancer.
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DOI：
10.3390/ijms19082438
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发表时间：
2018-08-18
影响因子：
5.6
通讯作者：
Ito K
中科院分区：
文献类型：
--
作者：
Fue M;Miki Y;Takagi K;Hashimoto C;Yaegashi N;Suzuki T;Ito K
松弛素在动物怀孕中起着重要作用，包括人类。这表明，松弛素诱导侵略性细胞生长和侵袭性的几种类型的癌症，包括子宫内膜癌。然而，松弛素的机制在很大程度上仍不清楚。在这项研究中，我们研究了松弛素2（RLN 2），在人类中的主要循环松弛素，对人子宫内膜癌细胞系的影响。RLN 2处理诱导HEC-1B和石川细胞的侵袭。通过转染松弛素受体1（RXFP 1）siRNA，RLN 2诱导的细胞侵袭显著降低。β-连环蛋白抑制剂XAV 939也显著抑制RLN 2诱导的细胞侵袭。RLN 2处理后，HEC-1B和石川细胞中钙粘蛋白表达降低，β-连环蛋白磷酸化水平升高。然后我们检测了80例子宫内膜样癌组织中RLN 2和RXFP 1的表达。RLN 2在子宫内膜癌细胞中呈阳性表达，且与组织学分级和RXFP 1呈相关性。这些结果表明，癌细胞中的粘附连接被钙粘蛋白/连环蛋白复合物的分解所削弱，这是由通过RLN 2/RXFP 1信号传导的β-连环蛋白磷酸化诱导的。
Relaxin is known to play an important role in animal pregnancies, including those of humans. It is suggested that relaxin induces aggressive cell growth and invasiveness in several types of cancer, including endometrial cancer. However, the mechanisms of relaxin remain largely unclear. In this study, we examined the effects of relaxin 2 (RLN2), the major circulating relaxin in humans, on human endometrial carcinoma cell lines. RLN2 treatment induced invasion in HEC-1B and Ishikawa cells. RLN2-induced cell invasion was significantly decreased by transfection of relaxin receptor 1 (RXFP1) siRNAs. The β-catenin inhibitor, XAV939, also significantly inhibited the RLN2-induced cell invasions. Both a decrease of cadherin expression and an increase of β-catenin phosphorylation were observed in response to the RLN2 treatment in HEC-1B and Ishikawa cells. We then examined RLN2 and RXFP1 expression in 80 human endometrioid endometrial carcinoma tissues. RLN2 immunoreactivity was detected in the human endometrial carcinoma cells and had a correlative tendency with histological grade and RXFP1. These results suggest that adherens junctions in cancer cells are weakened by the breakdown of the cadherin/catenin complex, which is induced by β-catenin phosphorylation via RLN2/RXFP1 signaling.
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