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下调的腺瘤性息肉病蛋白1通过抑制经典WNT信号通路抑制乳腺癌细胞侵袭。

APC downregulated 1 inhibits breast cancer cell invasion by inhibiting the canonical WNT signaling pathway.

作者信息

Cho Sung-Gook

机构信息

Department of Biotechnology, Korea National University of Transportation, Jeungpyeong, Chungbuk 368-701, Republic of Korea.

出版信息

Oncol Lett. 2017 Oct;14(4):4845-4852. doi: 10.3892/ol.2017.6801. Epub 2017 Aug 23.

DOI:10.3892/ol.2017.6801
PMID:29085490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5649524/
Abstract

Canonical WNT signaling promotes breast cancer progression. Although APC downregulated 1 (APCDD1) may inhibit canonical WNT signaling, its role in breast cancer remains to be fully understood. The present study demonstrated that APCDD1 suppressed breast cancer growth and metastasis by inhibiting canonical WNT signaling. The present study demonstrated that APCDD1 expression was negatively associated with breast cancer cell invasion, which was consistent with previous studies that indicated that APCDD1 expression was decreased in invasive ductal carcinoma compared with that in ductal carcinoma . Furthermore, APCDD1 expression was negatively associated with nuclear β-catenin expression and transcription factor/lymphoid enhancer binding factor 1 transcriptional activity in the present study. Silencing APCDD1 in non-invasive breast cancer cells using lentiviral APCDD1 short hairpin RNAs enhanced migration and invasion, which may be mediated by canonical WNT signaling, whereas the overexpression of human influenza hemagglutinin-tagged APCDD1 in invasive breast cancer cells repressed these properties. Therefore, the present study suggested that APCDD1 regulated breast cancer progression by targeting canonical WNT signaling and modulating breast cancer cell invasion.

摘要

经典WNT信号通路促进乳腺癌进展。尽管Apc下调基因1(APCDD1)可能抑制经典WNT信号通路,但其在乳腺癌中的作用仍有待充分了解。本研究表明,APCDD1通过抑制经典WNT信号通路抑制乳腺癌生长和转移。本研究表明,APCDD1表达与乳腺癌细胞侵袭呈负相关,这与先前的研究一致,即浸润性导管癌中APCDD1表达低于导管癌。此外,在本研究中,APCDD1表达与核β-连环蛋白表达以及转录因子/淋巴细胞增强因子结合因子1转录活性呈负相关。使用慢病毒APCDD1短发夹RNA沉默非侵袭性乳腺癌细胞中的APCDD1可增强迁移和侵袭,这可能由经典WNT信号通路介导,而在侵袭性乳腺癌细胞中过表达人流感血凝素标记的APCDD1可抑制这些特性。因此,本研究提示,APCDD1通过靶向经典WNT信号通路并调节乳腺癌细胞侵袭来调控乳腺癌进展。

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