Epithelial to mesenchymal transition (EMT) is a developmental event that is hijacked in some diseases such as fibrosis and cancer. In cancer, EMT has been linked to increased invasion and metastasis and is generally associated with a poor prognosis. In this study, we have compared phenotypic and functional differences between two isogenic cell lines with an EMT profile: D492M and D492HER2 that are both derived from D492, a breast epithelial cell line with stem cell properties. D492M is non-tumorigenic while D492HER2 is tumorigenic. Thus, the aim of this study was to analyze the expression profile of these cell lines, identify potential oncogenes, and evaluate their effects on cellular phenotype. We performed transcriptome and secretome analyses of D492M and D492HER2 and verified expression of selected genes at the RNA and protein level. One candidate, YKL-40 (also known as CHI3L1), was selected for further studies due to its differential expression between D492M and D492HER2, being considerably higher in D492HER2. YKL-40 has been linked to chronic inflammation diseases and cancer, yet its function is not fully understood. Knock-down experiments of YKL-40 in D492HER2 resulted in reduced migration and invasion as well as reduced ability to induce angiogenesis in an in vitro assay, plus changes in the EMT-phenotype. In summary, our data suggest that YKL-40 may provide D492HER2 with increased aggressiveness, supporting cancer progression and facilitating angiogenesis.

中文翻译：

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YKL-40 / CHI3L1促进过表达的HER2乳腺上皮祖细胞的迁移和侵袭，并为毛细血管样网络的形成产生利基。

上皮向间质转化（EMT）是一种发展事件，在某些疾病中被劫持，例如纤维化和癌症。在癌症中，EMT与侵袭和转移增加有关，通常与不良预后有关。在这项研究中，我们比较了两种具有EMT图谱的同基因细胞系：D492M和D492HER2之间的表型和功能差异，它们均来自具有干细胞特性的乳腺上皮细胞系D492。D492M没有致瘤性，而D492HER2是致瘤性的。因此，本研究的目的是分析这些细胞系的表达谱，鉴定潜在的癌基因，并评估其对细胞表型的影响。我们进行了D492M和D492HER2的转录组和分泌组分析，并在RNA和蛋白质水平上验证了所选基因的表达。由于其在D492M和D492HER2之间的差异表达（在D492HER2中要高得多），因此选择了一种候选物YKL-40（也称为CHI3L1）进行进一步研究。YKL-40与慢性炎症疾病和癌症有关，但其功能尚不完全清楚。在体外试验中，在D492HER2中进行YKL-40的基因敲除实验可减少迁移和侵袭，以及诱导血管生成的能力降低，以及EMT表型的改变。总而言之，我们的数据表明YKL-40可能为D492HER2提供增强的攻击性，支持癌症进展并促进血管生成。YKL-40与慢性炎症疾病和癌症有关，但其功能尚不完全清楚。在体外试验中，在D492HER2中进行YKL-40的基因敲除实验可减少迁移和侵袭，以及诱导血管生成的能力降低，以及EMT表型的改变。总而言之，我们的数据表明YKL-40可能为D492HER2提供增强的攻击性，支持癌症进展并促进血管生成。YKL-40与慢性炎症疾病和癌症有关，但其功能尚不完全清楚。在体外测定中，在D492HER2中进行YKL-40的基因敲除实验导致迁移和侵袭减少，诱导血管生成的能力降低，以及EMT表型发生变化。总而言之，我们的数据表明YKL-40可能为D492HER2提供增强的侵略性，支持癌症进展并促进血管生成。