定量蛋白质组学揭示 CD44 的敲低促进 Claudin-Low MDA-MB-231 和 Hs 578T 乳腺癌细胞系的增殖和迁移,Journal of Proteome Research

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定量蛋白质组学揭示 CD44 的敲低促进 Claudin-Low MDA-MB-231 和 Hs 578T 乳腺癌细胞系的增殖和迁移
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2021-06-02 , DOI: 10.1021/acs.jproteome.1c00293
Hyeyoon Kim _{1,

2,

3} , Jongmin Woo ₄ , Kisoon Dan ₃ , Kyung-Min Lee ₅ , Min-Sun Jin ₆ , In Ae Park _{1,

2} , Han Suk Ryu _{1,

2,

5} , Dohyun Han ₃

Affiliation

CD44 是一种跨膜糖蛋白，可以调节致癌过程。这被认为是乳腺癌 claudin-low 亚型的标志物，也是癌症干细胞标志物。然而，其在低密蛋白乳腺癌中的功能调节作用知之甚少。为了全面了解 CD44 的功能，我们对转染了 CD44 siRNA 的两种低密蛋白乳腺癌细胞系（MDA-MB-231 和 Hs 578T）进行了深入的基于串联质量标签的蛋白质组学分析。结果，我们观察到在 CD44 敲低的 MDA-MB-231 细胞中，2736 种蛋白质被上调，2172 种蛋白质被下调。对于 Hs 578T CD44 敲低细胞，412 种蛋白质被上调，443 种被下调。基因本体和网络分析表明，该标记的抑制介导与致癌细胞过程相关的重要功能改变，包括增殖、代谢、粘附和基因表达调控。一项功能研究证实，CD44 敲低通过调节与细胞周期、翻译和转录相关的基因的表达来抑制增殖。此外，这促进了多种细胞粘附相关蛋白的表达并减弱了癌细胞的迁移。最后，我们的蛋白质组学研究定义了 Claudin-low 乳腺癌细胞的 CD44 调节蛋白质组，揭示了介导细胞增殖和迁移的变化。

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Quantitative Proteomics Reveals Knockdown of CD44 Promotes Proliferation and Migration in Claudin-Low MDA-MB-231 and Hs 578T Breast Cancer Cell Lines

CD44 is a transmembrane glycoprotein that can regulate the oncogenic process. This is known to be a marker of the claudin-low subtype of breast cancer, as well as a cancer stem cell marker. However, its functional regulatory roles are poorly understood in claudin-low breast cancer. To gain comprehensive insight into the function of CD44, we performed an in-depth tandem mass tag-based proteomic analysis of two claudin-low breast cancer cell lines (MDA-MB-231 and Hs 578T) transfected with CD44 siRNA. As a result, we observed that 2736 proteins were upregulated and 2172 proteins were downregulated in CD44-knockdown MDA-MB-231 cells. For Hs 578T CD44-knockdown cells, 412 proteins were upregulated and 443 were downregulated. Gene ontology and network analyses demonstrated that the suppression of this marker mediates significant functional alterations related to oncogenic cellular processes, including proliferation, metabolism, adhesion, and gene expression regulation. A functional study confirmed that CD44 knockdown inhibited proliferation by regulating the expression of genes related to cell cycle, translation, and transcription. Moreover, this promoted the expression of multiple cell adhesion-associated proteins and attenuated cancer cell migration. Finally, our proteomic study defines the landscape of the CD44-regulated proteome of claudin-low breast cancer cells, revealing changes that mediate cell proliferation and migration. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD015171.

更新日期：2021-07-02

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