TMEPAI/PMEPA1 inhibits Wnt signaling by regulating beta-catenin stability and nuclear accumulation in triple negative breast cancer cells

Amalia Riezki; Abdelaziz Mohammed; Puteri Meidi Utami; Hwang Jongchan; Anwar Femmi; Watanabe Yukihide; Kato Mitsuyasu

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TMEPAI/PMEPA1 inhibits Wnt signaling by regulating beta-catenin stability and nuclear accumulation in triple negative breast cancer cells

机译：TMEPAI / PMEPA1通过调节三粘蛋白稳定性和三重阴性乳腺癌细胞中的核积累来抑制WNT信号传导

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Transmembrane prostate androgen-induced protein (TMEPAI) is a type I transmembrane protein induced by several intracellular signaling pathways such as androgen, TGF-beta, EGF, and Wnt signaling. It has been reported that TMEPAI functions to suppress TGF-beta and androgen signaling but here, we report a novel function of TMEPAI in Wnt signaling suppression. First, we show that TMEPAI significantly inhibits TCF/LEF transcriptional activity stimulated by Wnt3A, LiCl, and beta-catenin. Mechanistically, TMEPAI overexpression prevented beta-catenin accumulation in the nucleus and TMEPAI knockout in triple negative breast cancer cell lines promoted beta-catenin stability and nuclear accumulation together with increased mRNA levels of Wnt target genes AXIN2 and c-MYC. The presence of TGF-beta type I receptor kinase inhibitor did not affect the enhanced mRNA expression of AXIN2 in TMEPAI knockout cells. These data suggest that TMEPAI suppresses Wnt signaling by interfering with beta-catenin stability and nuclear translocation in a TGF-beta signaling-independent manner.

机译：跨膜前列腺诱导的蛋白质（TMepai）是由几种细胞内信号传导途径诱导的I型跨膜蛋白，例如雄激素，TGF-β，EGF和WNT信号传导。据报道，TMEPAI函数抑制TGF-β和雄激素信号，但在这里，我们在WNT信号抑制中报告了TMEPAI的新功能。首先，我们表明TMepai显着抑制Wnt3a，licl和β-catenin刺激的TCF / LEF转录活性。机械地，TMepai过表达阻止了三重阴性乳腺癌细胞中核和TMepai敲除的β-连环蛋白积聚，促进了β-连环蛋白稳定性和核积累以及Wnt靶基因轴和C-myc的增加水平。 TGF-β型I受体激酶抑制剂的存在并未影响TMepai敲除细胞中AXIN2的增强mRNA表达。这些数据表明TMepai通过干扰TGF-Beta信号传导的方式干扰β-catenin稳定性和核易位来抑制Wnt信号传导。

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来源
《Cellular Signalling》 |2019年第2019期|共10页
作者
Amalia Riezki; Abdelaziz Mohammed; Puteri Meidi Utami; Hwang Jongchan; Anwar Femmi; Watanabe Yukihide; Kato Mitsuyasu;
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作者单位

Univ Tsukuba Grad Sch Comprehens Human Sci Dept Expt Pathol 1-1-1 Tennodai Tsukuba Ibaraki 3058575 Japan;

Univ Tsukuba Grad Sch Comprehens Human Sci Dept Expt Pathol 1-1-1 Tennodai Tsukuba Ibaraki 3058575 Japan;

Univ Tsukuba Grad Sch Comprehens Human Sci Dept Expt Pathol 1-1-1 Tennodai Tsukuba Ibaraki 3058575 Japan;

Univ Tsukuba Grad Sch Comprehens Human Sci Dept Expt Pathol 1-1-1 Tennodai Tsukuba Ibaraki 3058575 Japan;

Univ Tsukuba Grad Sch Comprehens Human Sci Dept Expt Pathol 1-1-1 Tennodai Tsukuba Ibaraki 3058575 Japan;

Univ Tsukuba Grad Sch Comprehens Human Sci Dept Expt Pathol 1-1-1 Tennodai Tsukuba Ibaraki 3058575 Japan;

Univ Tsukuba Grad Sch Comprehens Human Sci Dept Expt Pathol 1-1-1 Tennodai Tsukuba Ibaraki 3058575 Japan;

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原文格式 PDF
正文语种 eng
中图分类细胞形态学;
关键词
TMEPAI; Wnt signaling; beta-catenin;

机译：Tmepai;wnt信号;beta-catenin;

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专利

1. TMEPAI/PMEPA1 inhibits Wnt signaling by regulating beta-catenin stability and nuclear accumulation in triple negative breast cancer cells [J] . Amalia Riezki, Abdelaziz Mohammed, Puteri Meidi Utami, Cellular Signalling . 2019,第期

机译：TMEPAI / PMEPA1通过调节三粘蛋白稳定性和三重阴性乳腺癌细胞中的核积累来抑制WNT信号传导
2. Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3 beta-regulated suppression of beta-catenin signaling [J] . Chen Yan, Chen Zong-yue, Chen Lin, Biochemical Pharmacology . 2019,第期

机译：Shikonin通过促进通过糖原合成酶激酶3β调节的β-catenin信号传导抑制上皮 - 间充质转化来抑制三阴性乳腺癌细胞转移
3. Schisandrin A inhibits triple negative breast cancer cells by regulating Wnt/ER stress signaling pathway [J] . Xu Xiaohong, Rajamanicham Vinothakumar, Xu Sujing, Biomedicine & pharmacotherapy =: Biomedecine & pharmacotherapie . 2019,第期

机译：Schisandrin A通过调节WNT / ER应力信号通路来抑制三重阴性乳腺癌细胞
4. Nanoparticles Coated with Frizzled7 Antibodies Enable Multivalent Binding for Enhanced Wnt Signaling Inhibition in Triple-Negative Breast Cancer [C] . Rachel S. Riley, Emily S. Day Society for Biomaterials annual meeting and exposition . 2018

机译：纳米颗粒涂有Frizzled7抗体使三价乳腺癌中增强Wnt信号抑制的多价结合。
5. Increased calcium intake regulates colonic CaSR expression and inhibits induced colitis and Wnt/beta-catenin signaling. [D] . Turki, Razan Anwar. 2013

机译：钙摄取的增加调节结肠CaSR的表达并抑制诱导的结肠炎和Wnt /β-catenin信号传导。
6. Wnt signaling blockage inhibits cell proliferation and migration and induces apoptosis in triple-negative breast cancer cells [O] . Birdal Bilir, Omer Kucuk, Carlos S Moreno 2013

机译：Wnt信号传导阻滞抑制细胞增殖和迁移并诱导三阴性乳腺癌细胞凋亡
7. Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells [O] . Birdal Bilir, Omer Kucuk, Carlos S Moreno 2013

机译：Wnt信号传导阻滞抑制细胞增殖和迁移，并诱导三阴性乳腺癌细胞凋亡

TMEPAI/PMEPA1 inhibits Wnt signaling by regulating beta-catenin stability and nuclear accumulation in triple negative breast cancer cells

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