UBC Theses and Dissertations
Caveolin-1 in cytoskeletal remodeling and metabolism in breast cancer cells Dickson, Fiona
Caveolin-1 (CAV1) is an integral membrane protein with previous roles defined in regulating both cancer cell migration and metabolism. Aberrant metabolism and migration are two of the many pathways that are associated with tumorigenesis and function to promote tumor cell growth, survival, and metastasis. Importantly, cell migration is energy-dependent and as a result, cancer metabolism and migration are closely linked. Using wildtype and CAV1 KO clonal cell lines, we show support that CAV1 regulates metabolism in MDA-MB-231 triple-negative breast cancer cells, a subtype of breast cancer that overexpresses CAV1. Compared to CAV1 KO cells, we found that wildtype cells expressing CAV1 displayed higher glycolytic activity and decreased mitochondrial respiration, correlating with a decrease in mitochondria abundance and exclusion of mitochondria from the cell periphery. Using metabolic inhibitors to target glycolysis and mitochondrial respiration, we next looked at the association of these metabolic pathways with actin remodeling and focal adhesion formation, which are closely associated with cell migration. Inhibition of glycolysis but not inhibition of mitochondrial respiration induced loss of F-actin, cell spreading, and significant cell death in both wildtype and CAV1 KO cells. Compared to CAV1 KO cells, wildtype cells expressing CAV1 displayed increased sensitivity to inhibition of glycolysis demonstrated by a more drastic loss of F-actin and increased cell spreading. Overall, these results suggest a role for CAV1 in promoting glycolytic metabolism in MDA-MB-231 cells. Additionally, it is shown here that MDA-MB-231 cells depend primarily on glycolysis and not mitochondrial respiration to maintain cell shape and cell survival and that CAV1 may be implicated in this dynamic.
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