p63-Mediated activation of the β-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis
p63-Mediated activation of the β-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis
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DOI：
10.1016/j.canlet.2014.07.016
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发表时间：
2014-10-10
期刊：
影响因子：
9.7
通讯作者：
Kim, Soo Mi
中科院分区：
文献类型：
--
作者：
Lee, Kwang Bok;Ye, Shuai;Kim, Soo Mi
食管鳞状细胞癌 (ESC) 的发生是多种基因改变的结果。我们之前的研究表明p63在人类ESC细胞中高表达并刺激其生长；然而，p63调节ESC细胞粘附和侵袭的机制仍不清楚。在本研究中，我们进一步阐明了p63调节ESC细胞转移的潜在分子机制。 p63 的敲低显着减少了 ESC 细胞系 TE-8 和 TE-12 的侵袭，而 p63 的过表达显着增加了 BE3 和 OE33 细胞的迁移率。在 p63 敲低的 ESC 细胞中，波形蛋白、twist、SUSD2 和 uPA 的 mRNA 和蛋白水平显着降低，而 p63 的过表达则诱导波形蛋白、SUSD2 和 uPA 的增加。此外，ESC细胞中p63的敲低显着降低了β-连环蛋白和c-Myc的水平，而p63的过表达增加了β-连环蛋白，但降低了p-β-连环蛋白水平。因此，p63通过激活β-catenin/c-Myc通路来调节ESC细胞的迁移和侵袭。我们的结果表明，靶向 p63 可能构成 ESC 的潜在治疗策略。 (C) 2014 Elsevier Ireland Ltd. 保留所有权利。
The development of esophageal squamous carcinomas (ESC) results from numerous genetic alterations. Our previous study demonstrated that p63 is highly expressed in human ESC cells and stimulates their growth; however, the mechanism by which p63 regulates ESC cell adhesion and invasion remains unclear. In the present study, we further elucidated the underlying molecular mechanisms by which p63 regulates metastasis in ESC cells. Knockdown of p63 significantly diminished the invasion of ESC cell lines TE-8 and TE-12, whereas overexpression of p63 significantly increased the migration rates of BE3 and OE33 cells. The mRNA and protein levels of vimentin, twist, SUSD2, and uPA were significantly decreased in p63-knockdown ESC cells, while overexpression of p63 induced an increase in vimentin, SUSD2, and uPA. In addition, knockdown of p63 in ESC cells significantly reduced levels of beta-catenin and c-Myc, while overexpression of p63 increased beta-catenin, but reduced p-beta-catenin level. Therefore, p63 regulates the migration and invasion of ESC cells through activation of the beta-catenin/c-Myc pathway. Our results suggest that targeting p63 may constitute a potential therapeutic strategy for ESC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.