Pyruvate Carboxylase Expression Modulates Primary Mammary Tumor Growth and Central Carbon Metabolism

Metabolic reprogramming is a fundamental requirement for triple-negative breast cancer’s (TNBC) growth and progression, with pyruvate carboxylase (PC) identified as a key mediator of breast cancer metastasis to the lung. Less is known, however, of PC’s role at the primary site. This study thus aimed to investigate the impact of PC suppression on primary tumor growth and if PC expression could inform the use of targeted metabolic therapies to augment currently used treatments for TNBC. Two separate PC knockdown cell lines revealed PC suppression to drive both a pro-tumor and anti-tumor effect, revealing a complex relationship between PC expression and tumor growth. PC suppressed M-Wnt cells in culture produced more lactate and had reduced rates of oxidative phosphorylation, rendering them more sensitive to lactate metabolism inhibition. This study highlights a dichotomous role for PC at the primary site that warrants additional investigation into utilizing PC to inform metabolic-based therapies.Master of Scienc