Thyroid hormone differentially modulates Warburg phenotype in breast cancer cells

被引:40
|
作者
Suhane, Sonal
Ramanujan, V. Krishnan [1 ]
机构
[1] Cedars Sinai Med Ctr, Dept Surg, Metab Photon Lab, Los Angeles, CA 90048 USA
基金
美国国家卫生研究院;
关键词
Breast cancer; Mitochondria; Warburg effect; Thyroid hormone; Bioenergetics; Chemotherapy; MITOCHONDRIA; RECEPTORS; DEMAND; KINASE;
D O I
10.1016/j.bbrc.2011.09.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:73 / 78
页数:6
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