Rab14 is overexpressed in ovarian cancers and promotes ovarian cancer proliferation through Wnt pathway (retracted article)
Rab14 is overexpressed in ovarian cancers and promotes ovarian cancer proliferation through Wnt pathway (retracted article)
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DOI：
10.1007/s13277-016-5420-4
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发表时间：
2016-12-01
期刊：
影响因子：
--
通讯作者：
Liu, Qifang
中科院分区：
文献类型：
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作者：
Hou, Rui;Jiang, Luo;Liu, Qifang
Rab GT3家族蛋白Rab 14与癌症发展有关。然而，其在卵巢癌中的临床意义及其生物学效应尚未研究。本研究旨在探讨Rab 14在卵巢癌进展中的临床意义、生物学作用和分子机制。我们用免疫组化方法检测了122例卵巢癌标本中Rab 14的表达模式，发现Rab 14过表达与FIGO分期相关（p = 0.0041）。我们使用siRNA去除SKOV 3细胞中的Rab 14，并在SW 626细胞中过表达Rab 14。Rab 14的敲低抑制细胞生长和侵袭，而其过表达促进细胞生长和侵袭。此外，Rab 14过表达增加了SW 626细胞对紫杉醇的耐药性，而其缺失降低了耐药性。然后，我们研究了Rab 14在WNT/β-catenin信号转导调节中的作用，证明Rab 14过表达调节GSK 3 β磷酸化和细胞核β-catenin积累。Rab 14缺失抑制TCF转录活性，过表达增强TCF转录活性，并相应改变Wnt靶基因MMP 7和c-myc。Wnt抑制剂可阻断Rab 14对细胞增殖和Wnt靶基因表达的影响。总之，本研究表明Rab 14至少部分通过Wnt信号通路促进卵巢癌细胞的侵袭性。
The Rab GTPase family protein Rab14 has been implicated in cancer development. However, its clinical significance in ovarian cancers and its biological effects have not been examined. The present study aims to examine the clinical significance, biological roles, and molecular mechanism of Rab14 in ovarian cancer progression. We examined expression pattern of Rab14 in 122 cases of ovarian cancer specimens using immunohistochemistry and found Rab14 overexpression correlated with FIGO stage (p = 0.0041). We depleted Rab14 in SKOV3 cells using siRNA and overexpressed Rab14 in SW626 cells. Knockdown of Rab14 inhibited cell growth and invasion while its overexpression facilitated cell growth and invasion. In addition, Rab14 overexpression increased paclitaxel resistance in SW626 cells while its depletion reduced drug resistance. Then, we investigated the role of Rab14 in the regulation of WNT/beta-catenin signaling, demonstrating Rab14 overexpression regulated GSK3 beta phosphorylation and nuclear beta-catenin accumulation. Rab14 depletion inhibited while its overexpression enhanced TCF transcriptional activity with corresponding change of Wnt target genes including MMP7 and c-myc. Wnt inhibitor abolished the effect of Rab14 on cell proliferation and Wnt target genes. In conclusion, the present study demonstrated that Rab14 promotes aggressiveness of ovarian cancer cell through, at least partly, Wnt signaling pathway.