Pyruvate Carboxylase Regulates Breast Cancer Growth and Metastasis Under Restricted Serine, Glycine, and Glutamine Conditions

Metabolic reprogramming has been identified as an important driver of breast cancer (BC) metastatic spread, particularly through upregulation of the anaplerotic enzyme pyruvate carboxylase (PC). We hypothesize that loss of PC will sensitize BC cells to additional metabolic alterations, primarily the restriction of serine, glycine, and glutamine. PC inhibition was modeled in metM-WntLung BC cells in vitro with siPC and shPC constructs. Cell viability and migration assays were conducted following exogenous serine and glycine restriction or glutaminase inhibition. Serine and glycine restriction reduced cell proliferation and metastasis in scramble conditions and targeted many prognostic biomarkers of metastasis. Similar responses were observed with glutaminase inhibition; however, PC loss did not contribute to impaired growth or metastasis. Ongoing work will assess this response in vivo with a surgical tumor resection model. This study therefore highlights altered metabolic reprogramming, particularly through depletion of nitrogen sources, as a potential therapeutic target for inhibiting BC metastatic spread.Master of Scienc