Dual Roles for Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) in Cancer Progression.
Dual Roles for Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) in Cancer Progression.
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DOI：
10.1007/5584_2016_50
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Miyazawa, Keiji
中科院分区：
文献类型：
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作者：
Hayakawa, Akira;Saitoh, Masao;Miyazawa, Keiji
上皮剪接调节蛋白 1 (ESRP1) 和 2 (ESRP2) 是 RNA 结合蛋白 hnRNP 家族的成员，可调节与上皮表型相关的选择性剪接事件。这些蛋白质在器官发生过程中发挥着至关重要的作用，包括颅面和表皮发育以及肺部和唾液腺的分支形态发生。最近的报告还探讨了它们在癌症进展过程中的作用。 ESRP 蛋白的表达在正常上皮中较低，但在原位癌和晚期癌中表达上调。有趣的是，它们在侵入性前沿中受到下调。 ESRP 表达的可塑性表明它们在癌症进展中发挥双重作用。一致地表明，ESRP 可抑制癌细胞的运动性和不依赖锚定的生长，同时通过增强对活性氧的抵抗力来支持细胞存活。最近出现了微调 ESRP 基因表达的调节电路。在这里，我们总结了 ESRP 对癌症进展发挥积极和消极影响的分子机制的最新发现。
Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) are members of the hnRNP family of RNA binding proteins that regulate alternative splicing events associated with epithelial phenotypes. These proteins play crucial roles during organogenesis, including craniofacial and epidermal development as well as branching morphogenesis in the lungs and salivary glands. Recent reports have also addressed their roles during cancer progression. Expression of ESRP proteins is low in normal epithelium but upregulated in carcinoma in situ and advanced carcinomas. Intriguingly, they are downregulated in invasive fronts. The plastic nature of ESRP expression suggests dual roles for them in cancer progression. Consistently, it has been shown that ESRPs suppress motility and anchorage-independent growth of cancer cells while supporting cell survival by enhancing resistance to reactive oxygen species. Regulatory circuits that fine-tune ESRP gene expression have recently emerged. Here, we summarize recent findings on the molecular mechanisms by which ESRPs exert positive as well as negative effects on cancer progression.