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Inhibiting EMT via glycolytic inhibition: therapeutic implications
Author(s) -
Gunsalus Kearney T.W.,
Dang Ngocly T.,
Schoenike Barry,
Wagoner Matthew P.,
Roopra Avtar
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.794.9
Subject(s) - glycolysis , warburg effect , epithelial–mesenchymal transition , metastasis , cancer research , biology , cancer cell , anaerobic glycolysis , breast cancer , cancer , microbiology and biotechnology , metabolism , biochemistry , genetics
Cancer cells are characterized by a heightened rate of glycolysis, a phenomenon known as the “Warburg Effect.” This increase in anaerobic respiration is one manifestation of the metabolic rigidity of transformed cells. Given that most mammalian cells have some ability to adapt to alterations in energy source, this lack of metabolic plasticity seen in cancers represents an attractive therapeutic target. Ninety percent of breast cancer mortalities can be attributed to metastasis, rather than the primary tumor per se. We therefore investigated the impact of targeting cancer cell metabolism using an in vitro model of metastasis. We find that although the absence of glycolysis has little effect on the growth and survival of cultured mammary epithelial cells in vitro , glycolytic inhibition had a potent impact on the epithelial to mesenchymal transition (EMT) normally induced by TGF‐β. Investigations into the molecular mechanisms behind the requirement for glycolysis during EMT suggest a role for the tumor suppressor NRSF and its metabolism‐sensing corepressor CtBP in regulating expression of pro‐metastatic genes such as SNAIL, SLUG and TWIST.