Kondaveeti Yuvabharath, Guttilla Reed Irene K, White Bruce A
Department of Cell Biology, University of Connecticut Heath Center, Farmington, CT 06030, USA.
Department of Biology, University of St. Joseph, West Hartford, CT 06117, USA.
Cancer Lett. 2015 Aug 1;364(1):44-58. doi: 10.1016/j.canlet.2015.04.025. Epub 2015 Apr 24.
Epithelial-mesenchymal transition (EMT) induces invasive properties in epithelial tumors and promotes metastasis. Although EMT-mediated cellular and molecular changes are well understood, very little is known about EMT-induced metabolic changes. HER2-positive BT-474 breast cancer cells were induced to undergo a stable EMT using mammosphere culture, as previously described by us for the ERα-positive MCF-7 breast cancer cells. Two epithelial breast cancer cell lines (BT-474 and MCF-7) were compared to their respective EMT-derived mesenchymal progeny (BT-474(EMT) and MCF-7(EMT)) for changes in metabolic pathways including glycolysis, glycogen metabolism, anabolic pathways and gluconeogenesis. Both EMT-derived cells displayed enhanced aerobic glycolysis along with the overexpression of specific glucose transporters, lactate dehydrogenase isoforms, monocarboxylate transporters and glycogen phosphorylase isoform. In contrast, both EMT-derived cells suppressed the expression of crucial enzymes in anabolic pathways and gluconeogenesis. STAT3, a transcription factor involved in tumor initiation and progression, plays a role in the EMT-related changes in the expression of specific enzymes and transporters. This study provides a broad overview of similar metabolic changes induced by EMT in two independent breast cancer cell lines. These metabolic changes may provide novel therapeutic targets for metastatic breast cancer.
上皮-间质转化（EMT）可诱导上皮性肿瘤的侵袭特性并促进转移。尽管EMT介导的细胞和分子变化已得到充分了解，但对于EMT诱导的代谢变化却知之甚少。如我们之前对雌激素受体α（ERα）阳性的MCF-7乳腺癌细胞所描述的那样，使用乳腺球培养法诱导HER2阳性的BT-474乳腺癌细胞发生稳定的EMT。将两种上皮性乳腺癌细胞系（BT-474和MCF-7）与其各自由EMT衍生的间充质子代细胞（BT-474(EMT)和MCF-7(EMT)）进行比较，以观察包括糖酵解、糖原代谢、合成代谢途径和糖异生在内的代谢途径变化。两种由EMT衍生的细胞均表现出有氧糖酵解增强，同时特定葡萄糖转运蛋白、乳酸脱氢酶同工型、单羧酸转运蛋白和糖原磷酸化酶同工型过表达。相反，两种由EMT衍生的细胞均抑制了合成代谢途径和糖异生中关键酶的表达。信号转导和转录激活因子3（STAT3）是一种参与肿瘤起始和进展的转录因子，在特定酶和转运蛋白表达的EMT相关变化中发挥作用。本研究全面概述了EMT在两种独立乳腺癌细胞系中诱导的类似代谢变化。这些代谢变化可能为转移性乳腺癌提供新的治疗靶点。
