SATB1 promotes prostate cancer metastasis by the regulation of epithelial-mesenchymal transition
SATB1 promotes prostate cancer metastasis by the regulation of epithelial-mesenchymal transition
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DOI：
10.1016/j.biopha.2016.01.038
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发表时间：
2016-04-01
影响因子：
7.5
通讯作者：
Shan, Yu-xi
中科院分区：
文献类型：
--
作者：
Mao, Li-jun;Yang, Chun-hua;Shan, Yu-xi
特异性富含AT序列结合蛋白1（SATB 1）在染色质结构和基因表达调控中起重要作用。最近的研究表明SATB 1的致癌作用。然而，SATB 1在前列腺癌进展和转移中的功能仍不清楚。本研究利用SATB 1表达载体或siRNA调控SATB 1在前列腺癌细胞和裸鼠移植瘤中的表达水平。对临床前列腺癌样品进行免疫组织化学分析。沉默SATB 1可抑制DU-145细胞裸鼠皮下移植瘤的生长，而过表达SATB 1可促进LNCaP细胞裸鼠皮下移植瘤的生长。免疫组织化学和Western blot分析表明，沉默SATB 1导致波形蛋白和MMP 2的表达减少，E-cadherin的表达增加，而SATB 1过表达导致波形蛋白和MMP 2的表达增加，E-cadherin的表达减少。与无转移前列腺癌和良性前列腺增生相比，有转移前列腺癌患者SATB 1、vimentin和MMP 2的表达显著增加，而E-cadherin的表达显著降低。综上所述，这些发现表明SATB 1对上皮-间质转化的调节可能有助于前列腺癌转移。(C)2016 Elsevier Masson SAS。All rights reserved.
Special AT-rich sequence binding protein 1 (SATB1) plays important role in the regulation of chromatin structure and gene expression. Recent studies have indicated oncogenic role of SATB1. However, the function of SATB1 in prostate cancer progression and metastasis remains unclear. In this study SATB1 expression vector or siRNA was employed to modulate the expression level of SATB1 in prostate cancer cells and xenograft tumor in nude mouse model. Immunohistochemical analysis was performed on clinical prostate cancer samples. Silencing SATB1 inhibited the growth of DU-145 cells subcutaneous tumor in nude mice, while SATB1 overexpression promoted the growth of LNCaP cells subcutaneous tumor in nude mice. Immunohistochemical and Western blot analysis of the xenografts showed that silencing SATB1 led to decreased expression of vimentin and MMP2 and increased expression of E-cadherin, while SATB1 overexpression led to increased expression of vimentin and MMP2 and decreased expression of E-cadherin. Furthermore, SATB1, vimentin and MMP2 expression was increased significantly while E-cadherin expression was reduced significantly in clinical samples of prostate carcinoma with metastasis compared to prostate carcinoma without metastasis and benign prostate hyperplasia. Taken together, these findings suggest that the modulation of epithelial-mesenchymal transition by SATB1 may contribute to prostate cancer metastasis. (C) 2016 Elsevier Masson SAS. All rights reserved.