Cancer Research UK - Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, UK.
BMC Cancer. 2023 Feb 14;23(1):153. doi: 10.1186/s12885-023-10581-3.
Epithelial-mesenchymal transition (EMT) is an embryonic programme implicated in cancer stem cells, metastasis and therapeutic resistance. Its role in cancer progression remains controversial because the transition can be partial or complete in different models and contexts.
Using human colon cancer DLD-1 cells, we engineered a cell line with a single-copy of Snail that was doxycycline-inducible and compared it to existing EMT models in DLD-1. The effect of Snail upregulation was characterised functionally, morphologically, and by transcriptional profiling and protein expression.
Induction with doxycycline increased Snail expression to a level similar to that observed in cancer cell lines spontaneously expressing Snail and results in partial EMT. In comparison, higher levels of overexpression arising from introduction of episomal-Snail, results in complete EMT. DLD-1 cells with partial EMT show chemoresistance in vitro, increased tumour growth in vivo and decreased apoptosis.
These findings highlight that the amount of bioavailable Snail can dictate phenotypic outcome and that partial EMT may be a preferred outcome of models operating within a natural range of Snail overexpression.
上皮-间充质转化（EMT）是一种与癌症干细胞、转移和治疗耐药性有关的胚胎程序。其在癌症进展中的作用仍存在争议，因为在不同的模型和环境中，这种转化可能是部分的或完全的。
我们使用人结肠癌细胞 DLD-1 构建了一个带有单个可诱导 Snail 拷贝的细胞系，并将其与 DLD-1 中的现有 EMT 模型进行了比较。通过功能、形态、转录谱和蛋白表达来描述 Snail 上调的影响。
用强力霉素诱导可将 Snail 的表达水平提高到与自发表达 Snail 的癌细胞系相似的水平，导致部分 EMT。相比之下，来自外源性-Snail 的过表达水平的增加导致完全 EMT。具有部分 EMT 的 DLD-1 细胞在体外表现出化疗耐药性，在体内肿瘤生长增加，凋亡减少。
这些发现强调了生物可利用的 Snail 的量可以决定表型结果，并且在自然范围内 Snail 过表达的模型中，部分 EMT 可能是首选的结果。
