The Ratio of RAC1B to RAC1 Expression in Breast Cancer Cell Lines as a Determinant of Epithelial/Mesenchymal Differentiation and Migratory Potential.
The Ratio of RAC1B to RAC1 Expression in Breast Cancer Cell Lines as a Determinant of Epithelial/Mesenchymal Differentiation and Migratory Potential.
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DOI：
10.3390/cells10020351
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发表时间：
2021-02-08
期刊：
影响因子：
6
通讯作者：
Ungefroren H
中科院分区：
文献类型：
--
作者：
Eiden C;Ungefroren H
乳腺癌（BC）是一种异质性疾病，包括具有不同组织形态学表型和转录定义亚型的肿瘤。然而，与表型多样性或转化相关或因果关系的非突变/表观遗传改变仍有待阐明。来自胰腺癌模型的数据表明，小 GTP 酶 RAC1 及其选择性剪接异构体 RAC1B 拮抗地控制转化生长因子 β 诱导的上皮-间质转化和细胞运动。使用一组已建立的具有分化良好的上皮细胞或分化不良的间充质表型的 BC 细胞系，我们观察了 RAC1B 和 RAC1 的亚型特异性蛋白表达。虽然上皮 BC 系为 RAC1B 高和 RAC1 低，但间充质系表现出相反的表达模式。高 RAC1B 和/或低 RAC1 丰度也与较差的侵袭潜力密切相关，反之亦然，正如通过测量随机细胞迁移（趋化作用）所揭示的那样，随机细胞迁移是已经历间充质转分化的细胞中细胞运动的首选模式。我们认为 BC 细胞中高 RAC1B:RAC1 比率可预测上皮表型，而低 RAC1B 和高 RAC1 是间充质状态的显着特征。 BC 患者肿瘤活检中 RAC1B 和 RAC1 的联合定量评估可能代表一种新的诊断工具，用于探测分子亚型并最终预测乳腺肿瘤的恶性潜力。
Breast cancer (BC) is a heterogenous disease encompassing tumors with different histomorphological phenotypes and transcriptionally defined subtypes. However, the non-mutational/epigenetic alterations that are associated with or causally involved in phenotype diversity or conversion remain to be elucidated. Data from the pancreatic cancer model have shown that the small GTPase RAC1 and its alternatively spliced isoform, RAC1B, antagonistically control epithelial–mesenchymal transition and cell motility induced by transforming growth factor β. Using a battery of established BC cell lines with either a well-differentiated epithelial or poorly differentiated mesenchymal phenotype, we observed subtype-specific protein expression of RAC1B and RAC1. While epithelial BC lines were RAC1Bhigh and RAC1low, mesenchymal lines exhibited the reverse expression pattern. High RAC1B and/or low RAC1 abundance also correlated closely with a poor invasion potential, and vice versa, as revealed by measuring random cell migration (chemokinesis), the preferred mode of cellular movement in cells that have undergone mesenchymal transdifferentiation. We propose that a high RAC1B:RAC1 ratio in BC cells is predictive of an epithelial phenotype, while low RAC1B along with high RAC1 is a distinguishing feature of the mesenchymal state. The combined quantitative assessment of RAC1B and RAC1 in tumor biopsies of BC patients may represent a novel diagnostic tool for probing molecular subtype and eventually predict malignant potential of breast tumors.
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