上皮间质可塑性（EMP）是癌症的一大特点。通过使细胞能够在不同形态和功能状态之间转变，EMP促进了侵袭、转移和治疗抵抗。我们报告了靠近二倍体的非癌变人类肺上皮细胞在无遗传改变的情况下自发地沿着EMP谱系进行转变。令人惊讶的是，超过一半的单细胞克隆体采用了间充质形态。我们独立地对上皮样和间充质样克隆体进行了表征。间充质克隆体失去上皮标志物，显示出较大的细胞长宽比和较低的运动性，大部分增殖率保持不变。干细胞标志物表达和代谢重塑独立于表型之外发生改变。在3D培养中，更多的上皮克隆体转化为间充质样。因此，在遗传改变和癌变转化之前，非癌变上皮细胞可能会获得与癌转移相关的特征。版权所有 © 2023。Elsevier Inc.出版。

Epithelial-mesenchymal plasticity (EMP) is a hallmark of cancer. By enabling cells to shift between different morphological and functional states, EMP promotes invasion, metastasis and therapy resistance. We report that near-diploid non-cancerous human epithelial lung cells spontaneously shift along the EMP spectrum without genetic changes. Strikingly, more than half of single cell-derived clones adopt a mesenchymal morphology. We independently characterise epithelial-like and mesenchymal-like clones. Mesenchymal clones lose epithelial markers, display larger cell aspect ratios and lower motility, with mostly unaltered proliferation rates. Stemness marker expression and metabolic rewiring diverge independently of phenotypes. In 3D culture, more epithelial clones become mesenchymal-like. Thus, non-cancerous epithelial cells may acquire cancer metastasis-associated features prior to genetic alterations and cancerous transformation.Copyright © 2023. Published by Elsevier Inc.