PMEPA1/TMEPAI isoforms function via its PY and Smad-interaction motifs for tumorigenic activities of breast cancer cells.,Genes to Cells

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PMEPA1/TMEPAI isoforms function via its PY and Smad-interaction motifs for tumorigenic activities of breast cancer cells.
Genes to Cells ( IF 1.3 ) Pub Date : 2020-03-17 , DOI: 10.1111/gtc.12766
Meidi U Puteri ₁ , Yukihide Watanabe ₁ , Bantari W K Wardhani _{1,

2} , Riezki Amalia _{1,

3} , Mohammed Abdelaziz _{1,

4} , Mitsuyasu Kato _{1,

5}

Affiliation

PMEPA1 (prostate transmembrane protein, androgen‐induced 1)/TMEPAI (transmembrane prostate androgen‐induced protein) is highly expressed in diverse cancers, including breast, lung and prostate cancers. It consists of four isoforms with distinct extracellular regions (isoforms a‐d). The expression and function of these isoforms are still poorly understood. Hence, we aimed to identify the preferentially expressed isoforms in breast cancer cells and analyze possible differences in tumorigenic functions. In this study, we used 5′ Rapid Amplification of cDNA Ends (RACE) and Western blot analyses to identify the mRNA variants and protein isoforms of TMEPAI and found that TMEPAI isoform d as the major isoform expressed by TGF‐β stimulation in breast cancer cells. We then generated CRISPR/Cas9‐mediated TMEPAI knockout (KO) breast cancer cell lines and used a lentiviral expression system to complement each isoform individually. Although there were no clear functional differences between isoforms, double PPxY (PY) motifs and a Smad‐interaction motif (SIM) of TMEPAI were both essential for colony and sphere formation. Collectively, our results provide a novel insight into TMEPAI isoforms in breast cancer cells and showed that coordination between double PY motifs and a SIM of TMEPAI are essential for colony and sphere formation but not for monolayer cell proliferation.

中文翻译：

PMEPA1 / TMEPAI亚型通过其PY和Smad相互作用基序对乳腺癌细胞的致癌活性起作用。

PMEPA1（前列腺跨膜蛋白，雄激素诱导的蛋白1）/ TMEPAI（跨膜前列腺雄激素诱导的蛋白）在多种癌症（包括乳腺癌，肺癌和前列腺癌）中高表达。它由四个具有不同细胞外区域的亚型组成（亚型a-d）。这些同工型的表达和功能仍然知之甚少。因此，我们旨在鉴定乳腺癌细胞中优先表达的同工型，并分析致瘤功能的可能差异。在这项研究中，我们使用cDNA末端5'快速扩增（RACE）和Western印迹分析来鉴定TMEPAI的mRNA变体和蛋白质同工型，并发现TMEPAI同工型d是TGF-β刺激在乳腺癌细胞中表达的主要同工型。。然后，我们生成了CRISPR / Cas9介导的TMEPAI敲除（KO）乳腺癌细胞系，并使用慢病毒表达系统来分别互补每个同种型。尽管同工型之间没有明显的功能差异，但TMEPAI的双PPxY（PY）基序和Smad相互作用基序（SIM）对菌落和球体形成都是必不可少的。总的来说，我们的结果为乳腺癌细胞中TMEPAI同工型提供了新颖的见解，并表明双PY基序和TMEPAI SIM之间的协调对于集落和球体形成至关重要，但对于单层细胞增殖则不是必需的。TMEPAI的两个PPxY（PY）基序和Smad相互作用基序（SIM）对菌落和球体的形成都是必不可少的。总的来说，我们的结果为乳腺癌细胞中TMEPAI同工型提供了新颖的见解，并表明双PY基序和TMEPAI SIM之间的协调对于集落和球体形成至关重要，但对于单层细胞增殖则不是必需的。TMEPAI的两个PPxY（PY）基序和Smad相互作用基序（SIM）对菌落和球体的形成都是必不可少的。总的来说，我们的结果为乳腺癌细胞中TMEPAI同工型提供了新颖的见解，并表明双PY基序和TMEPAI SIM之间的协调对于集落和球体形成至关重要，但对于单层细胞增殖则不是必需的。

更新日期：2020-03-17

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