Tan Zhijing, Nie Song, McDermott Sean P, Wicha Max S, Lubman David M
Department of Surgery, University of Michigan , Ann Arbor, Michigan 48109, United States.
Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory , Richland, Washington 99352, United States.
J Proteome Res. 2017 Feb 3;16(2):842-851. doi: 10.1021/acs.jproteome.6b00824. Epub 2017 Jan 20.
Cancers are initiated and developed from a small population of stem-like cells termed cancer stem cells (CSCs). There is heterogeneity among this CSC population that leads to multiple subpopulations with their own distinct biological features and protein expression. The protein expression and function may be impacted by amino acid variants that can occur largely due to single nucleotide changes. We have thus performed proteomic analysis of breast CSC subpopulations by mass spectrometry to study the presence of single amino acid variants (SAAVs) and their relation to breast cancer. We have used CSC markers to isolate pure breast CSC subpopulation fractions (ALDH+ and CD44+/CD24- cell populations) and the mature luminal cells (CD49f-EpCAM+) from the MCF-7 breast cancer cell line. By searching the Swiss-CanSAAVs database, 374 unique SAAVs were identified in total, where 27 are cancer-related SAAVs. 135 unique SAAVs were found in the CSC population compared with the mature luminal cells. The distribution of SAAVs detected in MCF-7 cells was compared with those predicted from the Swiss-CanSAAVs database, where we found distinct differences in the numbers of SAAVs detected relative to that expected from the Swiss-CanSAAVs database for several of the amino acids.
癌症由一小群被称为癌症干细胞(CSCs)的干细胞样细胞引发并发展而来。该癌症干细胞群体存在异质性,导致多个亚群具有各自独特的生物学特征和蛋白质表达。蛋白质表达和功能可能会受到氨基酸变体的影响,这些变体主要由单核苷酸变化产生。因此,我们通过质谱对乳腺癌干细胞亚群进行了蛋白质组学分析,以研究单氨基酸变体(SAAVs)的存在及其与乳腺癌的关系。我们使用癌症干细胞标志物从MCF-7乳腺癌细胞系中分离出纯的乳腺癌干细胞亚群组分(ALDH+和CD44+/CD24-细胞群体)以及成熟的管腔细胞(CD49f-EpCAM+)。通过搜索瑞士-加拿大单氨基酸变体数据库,总共鉴定出374个独特的单氨基酸变体,其中27个是与癌症相关的单氨基酸变体。与成熟的管腔细胞相比,在癌症干细胞群体中发现了135个独特的单氨基酸变体。将在MCF-7细胞中检测到的单氨基酸变体分布与从瑞士-加拿大单氨基酸变体数据库预测的分布进行比较,我们发现相对于瑞士-加拿大单氨基酸变体数据库对几种氨基酸的预期,检测到的单氨基酸变体数量存在明显差异。