Hairy/enhancer-of-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression.
Hairy/enhancer-of-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression.
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DOI：
10.1038/bjc.2015.84
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发表时间：
2015-03-31
影响因子：
8.8
通讯作者：
Komiya, S.
中科院分区：
文献类型：
--
作者：
Tsuru, A.;Setoguchi, T.;Matsunoshita, Y.;Nagao-Kitamoto, H.;Nagano, S.;Yokouchi, M.;Maeda, S.;Ishidou, Y.;Yamamoto, T.;Komiya, S.
关键词：
Notch途径的激活已在各种类型的癌症中报道。然而，与YRPW基序蛋白1（HEY 1）相关的毛状/分裂增强子在骨肉瘤中的作用尚不清楚。我们研究了HEY 1在骨肉瘤中的功能。研究HEY 1在人骨肉瘤中的表达。在体外和异种移植模型中评估HEY 1在骨肉瘤中的作用。此外，我们研究了作为HEY 1下游效应子的基质金属肽酶9（MMP 9）的功能。HEY 1在人骨肉瘤中表达上调。敲低HEY 1基因可抑制骨肉瘤细胞系的侵袭。相反，HEY 1的强制表达增加了间充质干细胞的侵袭性。此外，肺转移显着抑制敲低HEY 1。我们发现MMP 9是HEY 1的下游效应子，促进骨肉瘤细胞的侵袭。HEY 1的敲除降低了MMP9的表达。MMP9的加入挽救了骨肉瘤细胞的侵袭，这些细胞通过敲低HEY 1表达而变得侵袭性较低。我们的研究结果表明，HEY 1通过上调MMP 9的表达增加骨肉瘤的转移。因此，抑制HEY 1可能是预防骨肉瘤转移的一种新的治疗策略。
Activation of the Notch pathway has been reported in various types of cancers. However, the role of the hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) in osteosarcoma is unknown. We examined the function of HEY1 in osteosarcoma. Expression of HEY1 was studied in human osteosarcoma. The effects of HEY1 in osteosarcoma were evaluated in vitro and in a xenograft model. Moreover, we examined the function of matrix metallopeptidase 9 (MMP9) as a downstream effector of HEY1. HEY1 was upregulated in human osteosarcoma. Knockdown of HEY1 inhibited the invasion of osteosarcoma cell lines. In contrast, the forced expression of HEY1 increased the invasion of mesenchymal stem cell. In addition, lung metastases were significantly inhibited by the knockdown of HEY1. We found that MMP9 was a downstream effector of HEY1 that promotes the invasion of osteosarcoma cells. Knockdown of HEY1 decreased the expression of MMP9. Addition of MMP9 rescued the invasion of osteosarcoma cells that had been rendered less invasive by knockdown of HEY1 expression. Our findings suggested that HEY1 augmented the metastasis of osteosarcoma via upregulation of MMP9 expression. Therefore, inhibition of HEY1 may be a novel therapeutic strategy for preventing osteosarcoma metastasis.
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化疗对骨肉瘤细胞侵袭的抑制是由尿激酶纤溶酶原激活剂活性通过上调 EGR1 介导的。
影响因子：
3.7
作者：
Matsunoshita Y;Ijiri K;Ishidou Y;Nagano S;Yamamoto T;Nagao H;Komiya S;Setoguchi T
通讯作者：
Setoguchi T
影响因子：
4.6
作者：
Kokubo, Hiroki;Tomita-Miyagawa, Sachiko;Saga, Yumiko
通讯作者：
Saga, Yumiko
影响因子：
3.2
作者：
Hegyi, Marta;Semsei, Agnes F.;Kovacs, Gabor
通讯作者：
Kovacs, Gabor
DOI：
10.1006/bbrc.2000.3354
发表时间：
2000-08-28
影响因子：
3.1
作者：
Maier, MM;Gessler, M
通讯作者：
Gessler, M
影响因子：
4.8
作者：
Sakamoto, M;Hirata, H;Kageyama, R
通讯作者：
Kageyama, R