FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration

  • Authors:
    • Lan Zhou
    • Sufang Jiang
    • Qiang Fu
    • Kelly Smith
    • Kailing Tu
    • Hua Li
    • Yuhua Zhao
  • View Affiliations

  • Published online on: February 19, 2016     https://doi.org/10.3892/or.2016.4627
  • Pages: 2715-2722
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Abstract

Both fatty acid synthase (FASN) and ErbB2 have been shown to promote breast cancer cell migration. However, the underlying molecular mechanism remains poorly understood and there is no reported evidence that directly links glycolysis to breast cancer cell migration. In this study, we investigated the role of FASN, ErbB2-mediated glycolysis in breast cancer cell migration. First, we compared lactate dehydrogenase A (LDHA) protein levels, glycolysis and cell migration between FASN, ErbB2-overexpressing SK-BR-3 cells and FASN, ErbB2-low-expressing MCF7 cells. Then, SK-BR-3 cells were treated with cerulenin (Cer), an inhibitor of FASN, and ErbB2, LDHA protein levels, glycolysis, and cell migration were detected. Next, we transiently transfected ErbB2 plasmid into MCF7 cells and detected FASN, LDHA protein levels, glycolysis and cell migration. Heregulin-β1 (HRG-β1) is an activator of ErbB2 and 2-deoxyglucose (2-DG) and oxamate (OX) are inhibitors of glycolysis. MCF7 cells were treated with HRG-β1 alone, HRG-β1 plus 2-DG, OX or cerulenin and glycolysis, and cell migration were measured. We found that FASN, ErbB2-high-expressing SK-BR-3 cells displayed higher levels of glycolysis and migration than FASN, ErbB2-low-expressing MCF7 cells. Inhibition of FASN by cerulenin impaired glycolysis and migration in SK-BR-3 cells. Transient overexpression of ErbB2 in MCF7 cells promotes glycolysis and migration. Moreover, 2-deoxyglucose (2-DG), oxamate (OX), or cerulenin partially reverses heregulin-β1 (HRG-β1)-induced glycolysis and migration in MCF7 cells. In conclusion, this study demonstrates that FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration. These novel findings indicate that targeting FASN, ErbB2-mediated glycolysis may be a new approach to reverse breast cancer cell migration.
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May-2016
Volume 35 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhou L, Jiang S, Fu Q, Smith K, Tu K, Li H and Zhao Y: FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration. Oncol Rep 35: 2715-2722, 2016
APA
Zhou, L., Jiang, S., Fu, Q., Smith, K., Tu, K., Li, H., & Zhao, Y. (2016). FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration. Oncology Reports, 35, 2715-2722. https://doi.org/10.3892/or.2016.4627
MLA
Zhou, L., Jiang, S., Fu, Q., Smith, K., Tu, K., Li, H., Zhao, Y."FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration". Oncology Reports 35.5 (2016): 2715-2722.
Chicago
Zhou, L., Jiang, S., Fu, Q., Smith, K., Tu, K., Li, H., Zhao, Y."FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration". Oncology Reports 35, no. 5 (2016): 2715-2722. https://doi.org/10.3892/or.2016.4627