2. Academic Validation
  3. GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity

GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity

  • Cell Chem Biol. 2016 May 19;23(5):567-578. doi: 10.1016/j.chembiol.2016.03.017.
Sharon M Louie 1,  Elizabeth A Grossman 1,  Lisa A Crawford 2,  Lucky Ding 1,  Roman Camarda 3,  Tucker R Huffman 1,  David K Miyamoto 1,  Andrei Goga 3,  Eranthie Weerapana 2,  Daniel K Nomura 4
Affiliations

Affiliations

  • 1 Departments of Chemistry and Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • 2 Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA.
  • 3 Department of Cell and Tissue Biology and Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 4 Departments of Chemistry and Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: [email protected].
PMID: 27185638 DOI: 10.1016/j.chembiol.2016.03.017
Abstract

Breast cancers possess fundamentally altered metabolism that fuels their pathogenicity. While many metabolic drivers of breast cancers have been identified, the metabolic pathways that mediate breast Cancer malignancy and poor prognosis are less well understood. Here, we used a reactivity-based chemoproteomic platform to profile metabolic enzymes that are enriched in breast Cancer cell types linked to poor prognosis, including triple-negative breast Cancer (TNBC) cells and breast Cancer cells that have undergone an epithelial-mesenchymal transition-like state of heightened malignancy. We identified glutathione S-transferase Pi 1 (GSTP1) as a novel TNBC target that controls Cancer pathogenicity by regulating glycolytic and lipid metabolism, energetics, and oncogenic signaling pathways through a protein interaction that activates glyceraldehyde-3-phosphate dehydrogenase activity. We show that genetic or pharmacological inactivation of GSTP1 impairs cell survival and tumorigenesis in TNBC cells. We put forth GSTP1 inhibitors as a novel therapeutic strategy for combatting TNBCs through impairing key Cancer metabolism and signaling pathways.

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