Assessing metastatic potential of breast cancer cells based on EGFR dynamics
Assessing metastatic potential of breast cancer cells based on EGFR dynamics
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DOI：
10.1038/s41598-018-37625-0
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发表时间：
2019-03-04
影响因子：
4.6
通讯作者：
Yeh, Hsin-Chih
中科院分区：
文献类型：
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作者：
Liu, Yen-Liang;Chou, Chao-Kai;Yeh, Hsin-Chih
脱轨的跨膜受体运输可能是肿瘤发生和肿瘤侵袭性增加的标志，但受体动力学尚未用于区分转移性癌细胞和侵袭性较低的癌细胞。本研究采用单粒子示踪技术，建立了一种名为跨膜受体动力学（Transmembrane Receptor Dynamics，TReD）的表型分析方法，研究了表皮生长因子受体（epidermal growth factor receptor，EGFR）在7种乳腺上皮细胞系中的动力学，并建立了一种名为跨膜受体动力学（Transmembrane Receptor Dynamics，TReD）的表型分析方法。在这里，我们显示了一个明确的证据，增加EGFR扩散率和扩大EGFR限制在质膜（PM）的大小与这些细胞系的转移潜力增强。通过比较TReD结果与基因表达谱，我们发现EGFR扩散率与乳腺癌管腔分化评分之间存在明显的负相关性（r = -0.75）。在诱导上皮-间充质转化（EMT）后，EGFR扩散率对于非致瘤性MCF 10A（99%）和非侵袭性MCF 7（56%）细胞显著增加，但对于高转移性MDA-MB-231细胞不显著增加。我们认为，肌动蛋白丝在EMT的重组修改PM结构，导致受体动力学的变化。因此，TReD可以作为一种新的生物物理标志物来探测癌细胞的转移潜力，甚至监测转移的转变。
Derailed transmembrane receptor trafficking could be a hallmark of tumorigenesis and increased tumor invasiveness, but receptor dynamics have not been used to differentiate metastatic cancer cells from less invasive ones. Using single-particle tracking techniques, we developed a phenotyping asssay named Transmembrane Receptor Dynamics (TReD), studied the dynamics of epidermal growth factor receptor (EGFR) in seven breast epithelial cell lines and developed a phenotyping assay named Transmembrane Receptor Dynamics (TReD). Here we show a clear evidence that increased EGFR diffusivity and enlarged EGFR confinement size in the plasma membrane (PM) are correlated with the enhanced metastatic potential in these cell lines. By comparing the TReD results with the gene expression profiles, we found a clear negative correlation between the EGFR diffusivities and the breast cancer luminal differentiation scores (r = -0.75). Upon the induction of epithelial-mesenchymal transition (EMT), EGFR diffusivity significantly increased for the non-tumorigenic MCF10A (99%) and the non-invasive MCF7 (56%) cells, but not for the highly metastatic MDA-MB-231 cell. We believe that the reorganization of actin filaments during EMT modified the PM structures, causing the receptor dynamics to change. TReD can thus serve as a new biophysical marker to probe the metastatic potential of cancer cells and even to monitor the transition of metastasis.