Analysis of lipid metabolism regulators in breast cancer cells after induction of the Epithelial to Mesenchymal Transition

Abstract

The process of tumor metastasis is often enabled by the epithelial-mesenchymal transition (EMT), a key developmental program that is often activated during cancer invasion and metastasis. During the EMT process, cells undergo phenotypic changes, lose of E-cadherin expression and acquire invasive properties that allow them to migrate through the extracellular matrix. EMT inducers or regulators have been shown to induce cancer cells to form populations with cancer stem cell-like characteristics, providing them with therapeutic resistance and conferred tumor recurrence. Although metabolism plays a fundamental role in essentially every function of a cell, little is known about how the EMT programme involves in regulating cell’s metabolism contributes to the morphological and molecular changes. An early and universal feature of tumors is the activation of lipid metabolism, and it is a central hallmark of many cancers including prostate and breast cancer. To understand lipid metabolism in cancer, we used LC-MS to identify lipid construct. Interestingly, after induction of EMT phenotype, cells show global fatty acid metabolism changes. We found that peroxisome proliferator activated receptor-gamma (PPAR-γ), a master transcriptional regulator of adipogenesis, was downregulated during EMT process. Downregulation of PPAR-γ in breast cancer cells enhances cell migration, colony formation, and chemotherapy resistance indicating PPAR-γ has critical role in breast cancer metastasis.