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首页> 外文期刊>Molecular Carcinogenesis >Downregulation of HDPR1 is associated with poor prognosis and affects expression levels of p120-catenin and beta-catenin in nonsmall cell lung cancer.
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Downregulation of HDPR1 is associated with poor prognosis and affects expression levels of p120-catenin and beta-catenin in nonsmall cell lung cancer.

机译：HDPR1的下调与不良预后相关，并影响非小细胞肺癌中p120-catenin和β-catenin的表达水平。

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摘要

HDPR1 (human homologue of Dapper) is considered as a Dishevelled (DVL) antagonist in WNT signaling. We recently reported that DVL was associated with cytoplasmic accumulation of beta-catenin in nonsmall cell lung cancer (NSCLC). Whether cytoplasmic accumulation of beta-catenin is correlated with HDPR1 is unclear. Xenopus Dapper (XDpr) was found to stabilize p120-catenin (p120ctn) in Xenopus embryogenesis. However, whether HDPR1 can regulate p120ctn expression level is not reported. Furthermore, how HDPR1 influences invasiveness in lung carcinogenesis is also not well understood. In this study, our aims were to explore the effects of HDPR1 on the lung carcinogenesis and to examine the relationship among HDPR1, beta-catenin, and p120ctn. Immunohistochemical analysis in 120 NSCLC tissues showed that HDPR1 was significantly lower in 82 specimens (68.3%). Reverse transcription (RT)-polymerase chain reaction (PCR) and Western blotting analysis showed that the mRNA and protein expression of HDPR1 were lower in tumor tissues as compared to corresponding nontumorous tissues. Moreover, reduced HDPR1 expression was related to the clinicopathological factors and was an independent risk factor for prognosis of the patients with NSCLC. In addition, HDPR1 expression was also associated with the expression of p120ctn and beta-catenin in lung cancer tissues. Knockdown of HDPR1 gene enhanced the invasive ability of lung cancer cells, which was dependent on p120ctn and independent of beta-catenin. In conclusion, the function of HDPR1 on regulating p120ctn may play an important role in human lung carcinogenesis. Restoration of HDPR1 gene may be a new therapeutic target of lung cancer.
机译：HDPR1（Dapper的人类同源物）被认为是WNT信号传导中的Disheveled（DVL）拮抗剂。我们最近报道了DVL与非小细胞肺癌（NSCLC）中β-catenin的细胞质积累有关。尚不清楚β-catenin的细胞质积累是否与HDPR1相关。发现非洲爪蟾（XDpr）可以稳定非洲爪蟾胚胎发生中的p120-catenin（p120ctn）。但是，没有报道HDPR1是否可以调节p120ctn表达水平。此外，HDPR1如何影响肺癌发生过程中的浸润性也还不清楚。在这项研究中，我们的目的是探讨HDPR1对肺癌的影响，并检查HDPR1，β-catenin和p120ctn之间的关系。在120个NSCLC组织中进行的免疫组织化学分析显示，在82个标本中，HDPR1显着降低（68.3％）。逆转录（RT）-聚合酶链反应（PCR）和蛋白质印迹分析表明，与相应的非肿瘤组织相比，肿瘤组织中HDPR1的mRNA和蛋白表达较低。此外，HDPR1表达降低与临床病理因素有关，并且是NSCLC患者预后的独立危险因素。此外，HDPR1表达还与肺癌组织中p120ctn和β-catenin的表达相关。剔除HDPR1基因可增强肺癌细胞的侵袭能力，这依赖于p120ctn并独立于β-catenin。总之，HDPR1调节p120ctn的功能可能在人类肺癌发生中起重要作用。 HDPR1基因的恢复可能是肺癌的一个新的治疗目标。

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