Metformin Targets Cholesterol Biosynthesis Pathway, GM1 Lipid Raft Stabilization, EGFR Signaling and Proliferation in Triple Negative Breast Cancers

Reema S Wahdan-Alaswad, Hiba S Salem, Susan M Edgerton, and Ann D Thor
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Ann D Thor: Department of Pathology, University of Colorado Anschutz Medical Campus, USA

Cancer Therapy & Oncology International Journal, 2018, vol. 9, issue 3, 89-98

Abstract: Triple negative breast cancer (TNBC) cells are particularly dependent on dysregulation of carbohydrate and lipid metabolism. We have demonstrated that the anti†diabetic agent metformin is particularly effective against TNBC, inhibiting proliferation, motility, pro†carcinogenic signaling, fatty acid synthesis and reducing the cancer stem cell subpopulation. In this study we evaluated the downstream effects of metformin on lipid metabolism and subcellular functions, using human derived TNBC cells MDA†MB†468, MDA†MB†231, BT-549 and HCC†70. Metformin inhibited transcription and translation of over 20 genes/enzymes in the cholesterol biosynthesis pathway, including HMG†CoA, a critical rate†limiting step in cholesterol synthesis and the target of statin drugs. It also down regulates cholesterol/GM1 incorporation into the cell membrane, destabilizes GM1 but not caveolin lipid rafts and down-regulates EGFR expression, activation and signaling (dependent in part on GM1 raft localization).

Keywords: juniper publishers:oncology journals; oncology research journals; oncology journal articles; oncology and cancer case reports; oncology journal of clinical and experimental cancer research; open access; open access journals; Oncology International Journal; juniper publishers reivew (search for similar items in EconPapers)
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:adp:jctoij:v:9:y:2018:i:3:p:89-98

DOI: 10.19080/CTOIJ.2018.09.555765

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