Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial-mesenchymal transition in triple-negative breast cancer.

Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial-mesenchymal transition in triple-negative breast cancer.
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Prrx1b 沉默可抑制三阴性乳腺癌中的细胞增殖、迁移、侵袭和上皮间质转化。

DOI:
10.1111/jcmm.12856
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发表时间:
2016-09
影响因子:
5.3
通讯作者:
Wang HB
Wang HB
中科院分区:
医学2区
文献类型:
--
作者:
Lv ZD;Yang ZC;Liu XP;Jin LY;Dong Q;Qu HL;Li FN;Kong B;Sun J;Zhao JJ;Wang HB

文献摘要

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三阴性乳腺癌(TNBC)是一种高度侵袭性的肿瘤亚型,预后较差。TNBC进展的机制在很大程度上仍然未知。迄今为止,还没有针对这种肿瘤亚型的有效治疗靶点。配对相关同源盒1b (Prrx1b)是Prrx1的主要亚型之一,已被确定为一种新的上皮-间质转化(EMT)诱导剂。然而,Prrx1b在TNBC中的功能尚未被阐明。在这项研究中,我们发现Prrx1b在TNBC中显著上调,并与肿瘤大小和乳腺癌血管浸润相关。Prrx1b的沉默抑制基底样癌细胞的增殖、迁移和侵袭。此外,Prrx1b的沉默阻止了Wnt/β‐catenin信号通路并诱导了间充质-上皮转化(MET)。综上所述,我们的数据表明Prrx1b可能是TNBC细胞中EMT的重要调节因子,也是干预TNBC侵袭和转移的新治疗靶点。
Triple‐negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The mechanisms involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumour subtype. Paired‐related homeobox 1b (Prrx1b), one of major isoforms of Prrx1, has been identified as a new epithelial–mesenchymal transition (EMT) inducer. However, the function of Prrx1b in TNBC has not been elucidated. In this study, we found that Prrx1b was significantly up‐regulated in TNBC and associated with tumour size and vascular invasion of breast cancer. Silencing of Prrx1b suppressed the proliferation, migration and invasion of basal‐like cancer cells. Moreover, silencing of Prrx1b prevented Wnt/β‐catenin signaling pathway and induced the mesenchymal‐epithelial transition (MET). Taken together, our data indicated that Prrx1b may be an important regulator of EMT in TNBC cells and a new therapeutic target for interventions against TNBC invasion and metastasis.