Balcik-Ercin Pelin, Cayrefourcq Laure, Soundararajan Rama, Mani Sendurai A, Alix-Panabières Catherine
Department of Molecular Biology and Genetics, Gebze Technical University, Kocaeli 41400, Turkey.
Laboratory of Rare Human Circulating Cells, University Medical Center of Montpellier, 34093 Montpellier, France.
Cancers (Basel). 2021 Oct 28;13(21):5408. doi: 10.3390/cancers13215408.
Metastasis is a complicated and only partially understood multi-step process of cancer progression. A subset of cancer cells that can leave the primary tumor, intravasate, and circulate to reach distant organs are called circulating tumor cells (CTCs). Multiple lines of evidence suggest that in metastatic cancer cells, epithelial and mesenchymal markers are co-expressed to facilitate the cells' ability to go back and forth between cellular states. This feature is called epithelial-to-mesenchymal plasticity (EMP). CTCs represent a unique source to understand the EMP features in metastatic cascade biology. Our group previously established and characterized nine serial CTC lines from a patient with metastatic colon cancer. Here, we assessed the expression of markers involved in epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transition in these unique CTC lines, to define their EMP profile. We found that the oncogenes MYC and ezrin were expressed by all CTC lines, but not SIX1, one of their common regulators (also an EMT inducer). Moreover, the MET activator GRHL2 and its putative targets were strongly expressed in all CTC lines, revealing their plasticity in favor of an increased MET state that promotes metastasis formation.
转移是癌症进展过程中一个复杂且仅部分为人所知的多步骤过程。能够离开原发性肿瘤、进入血管并循环至远处器官的一部分癌细胞被称为循环肿瘤细胞（CTC）。多条证据表明，在转移性癌细胞中，上皮和间充质标志物会共同表达，以促进细胞在不同细胞状态之间来回转换的能力。这一特性被称为上皮-间充质可塑性（EMP）。CTC是了解转移级联生物学中EMP特征的独特来源。我们团队之前从一名转移性结肠癌患者身上建立并鉴定了九条连续的CTC系。在此，我们评估了这些独特的CTC系中参与上皮-间充质转化（EMT）和间充质-上皮转化（MET）的标志物的表达情况，以确定它们的EMP特征。我们发现，致癌基因MYC和埃兹蛋白在所有CTC系中均有表达，但它们的共同调节因子之一（也是一种EMT诱导剂）SIX1却没有表达。此外，MET激活剂GRHL2及其假定靶点在所有CTC系中均强烈表达，这揭示了它们的可塑性，有利于增加促进转移形成的MET状态。
