CDK12 Promotes Breast Cancer Progression and Maintains Stemness by Activating c-myc/β -catenin Signaling

doi:10.2174/1568009619666191118113220

摘要

背景：CDK12是具有有效维持癌细胞干性能力的乳腺癌的有希望的治疗靶标。目的：我们旨在研究CDK12维持乳腺癌干性的机制。方法：通过RT-qPCR和IHC检测CDK12表达水平。然后建立CDK12改变的乳腺癌细胞系MDA-MB-231-shCDK12和SkBr-3-CDK12。使用CCK8，集落形成测定法和异种移植模型来评估CDK12对致瘤性的影响。确定了Transwell测定法，乳球形成，FACS和体内肺转移模型。蛋白质印迹进一步通过c-myc /β-catenin途径表征CDK12在乳腺癌干中的机制。结果：我们的结果显示乳腺癌样品中CDK12的含量较高。在CDK12high组中，肿瘤形成，癌细胞移动性，球体形成和上皮-间质转化将得到增强。此外，CDK12与肺转移有关，并维持乳腺癌细胞的干性。与CDK12low细胞相比，CDK12high癌细胞具有更高的致瘤性和CD44 +亚群。我们的研究表明c-myc与CDK12阳性表达。 CDK12激活c-myc /β-catenin信号传导，这是启动乳腺癌干细胞更新的潜在机制，并可能成为乳腺癌预后的潜在生物标志物。结论：CDK12的过表达通过激活c-myc /β-catenin信号传导促进乳腺癌的肿瘤发生并维持乳腺癌的干性。抑制CDK12表达可能成为乳腺癌的潜在疗法。

关键词: 乳腺癌，干癌，转移瘤，CDK12，c-myc，β-catenin。

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DOI https://dx.doi.org/10.2174/1568009619666191118113220	Print ISSN 1568-0096
Publisher Name Bentham Science Publisher	Online ISSN 1873-5576

当代肿瘤药物靶点

CDK12通过激活c-myc /β-catenin信号传导促进乳腺癌的进展并保持茎直

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图形摘要

当代肿瘤药物靶点

CDK12通过激活c-myc /β-catenin信号传导促进乳腺癌的进展并保持茎直

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