The SKBR3 cell-membrane proteome reveals telltales of aberrant cancer cell proliferation and targets for precision medicine applications.
The SKBR3 cell-membrane proteome reveals telltales of aberrant cancer cell proliferation and targets for precision medicine applications.
复制标题
DOI：
10.1038/s41598-022-14418-0
复制
发表时间：
2022-06-27
影响因子：
4.6
通讯作者：
Lazar, Iulia M.
中科院分区：
文献类型：
--
作者：
Karcini, Arba;Lazar, Iulia M.
质膜蛋白质组位于细胞外和细胞内环境之间的界面，并通过其在信号转导、免疫识别、营养转运和细胞-细胞/细胞-基质相互作用中的各种作用，在决定细胞命运方面发挥着绝对关键的作用。我们的工作旨在探索HER 2+乳腺癌细胞系（SKBR 3）的细胞膜蛋白质组，以确定负责不受控制的细胞增殖的触发因素以及能够进行检测和治疗干预的内在资源。为了模拟使癌细胞能够进化适应/存活性状的环境条件，在富含血清和缺乏血清的条件下进行细胞培养。蛋白质组学分析能够鉴定约2000种细胞膜蛋白。分类为具有受体/酶活性的蛋白质、CD抗原、转运蛋白和细胞粘附/连接蛋白揭示了在驱动细胞生长、凋亡、分化、免疫应答、粘附和迁移以及增殖的替代途径的过程中的重叠作用。大量的肿瘤标志物（> 50）和推定的药物靶标（> 100）暴露了尚未探索的检测和靶向机会的巨大潜力，而15种抗原免疫学标志物的存在使得能够评估上皮、间充质或干细胞特征。血清饥饿的细胞显示线粒体OXPHOS/ATP合成，蛋白质折叠和定位相关的过程改变，而血清处理的细胞表现出支持组织侵袭和转移的属性。总而言之，我们的研究结果推进了对维持异常癌细胞增殖、存活和对治疗药物产生耐药性的生物触发因素的理解，并揭示了指导免疫学分析和精准医学应用的巨大先天机会，这些应用旨在靶点选择或药物发现。
The plasma membrane proteome resides at the interface between the extra- and intra-cellular environment and through its various roles in signal transduction, immune recognition, nutrient transport, and cell–cell/cell–matrix interactions plays an absolutely critical role in determining the fate of a cell. Our work was aimed at exploring the cell-membrane proteome of a HER2+ breast-cancer cell line (SKBR3) to identify triggers responsible for uncontrolled cell proliferation and intrinsic resources that enable detection and therapeutic interventions. To mimic environmental conditions that enable cancer cells to evolve adaptation/survival traits, cell culture was performed under serum-rich and serum-deprived conditions. Proteomic analysis enabled the identification of ~ 2000 cell-membrane proteins. Classification into proteins with receptor/enzymatic activity, CD antigens, transporters, and cell adhesion/junction proteins uncovered overlapping roles in processes that drive cell growth, apoptosis, differentiation, immune response, adhesion and migration, as well as alternate pathways for proliferation. The large number of tumor markers (> 50) and putative drug targets (> 100) exposed a vast potential for yet unexplored detection and targeting opportunities, whereas the presence of 15 antigen immunological markers enabled an assessment of epithelial, mesenchymal or stemness characteristics. Serum-starved cells displayed altered processes related to mitochondrial OXPHOS/ATP synthesis, protein folding and localization, while serum-treated cells exhibited attributes that support tissue invasion and metastasis. Altogether, our findings advance the understanding of the biological triggers that sustain aberrant cancer cell proliferation, survival and development of resistance to therapeutic drugs, and reveal vast innate opportunities for guiding immunological profiling and precision medicine applications aimed at target selection or drug discovery.
登录
查看更多内容
DOI：
10.1073/pnas.1808790115
发表时间：
2018-11-13
影响因子：
11.1
作者：
Bausch-Fluck D;Goldmann U;Müller S;van Oostrum M;Müller M;Schubert OT;Wollscheid B
通讯作者：
Wollscheid B
间隙连接和癌症：沟通50年。
DOI：
10.1038/nrc.2016.105
发表时间：
2016-12
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Aasen T;Mesnil M;Naus CC;Lampe PD;Laird DW
通讯作者：
Laird DW
影响因子：
16.6
作者：
Baker MS;Ahn SB;Mohamedali A;Islam MT;Cantor D;Verhaert PD;Fanayan S;Sharma S;Nice EC;Connor M;Ranganathan S
通讯作者：
Ranganathan S
影响因子：
--
作者：
Bendas G;Borsig L
通讯作者：
Borsig L
影响因子：
4.4
作者：
Hoermann, Katrin;Stukalov, Alexey;Bennettt, Keiryn L.
通讯作者：
Bennettt, Keiryn L.