G1P3, a mitochondrial localized protein, induces mtROS to promote cell migration through Caveolin 1

Metastasis is the leading cause of deaths in > 90% of breast cancer patients. We reported that G1P3-induced mitochondrial reactive oxygen species (mtROS) promotes breast cancer metastasis. Although G1P3 was suggested as a mitochondrial protein, its submitochondrial localization was inconclusive. Trypsin digestion and sodium carbonate extraction studies of pure mitochondria confirmed G1P3 as an integral membrane protein within the mitochondria. Gene expression analysis identified upregulation of Caveolin 1, an endocytic regulator, by 4-fold in G1P3 overexpressing cells (MCF-7/G1P3) (p≤0.05). We hypothesized that G1P3-induced mtROS leads to upregulation of Cav-1 and confers migratory potential in breast cancer cells. Consistent with this, abrogation of mtROS downregulated Cav-1 expression and reduced the migration of MCF-7/G1P3 cells (p≤0.05). Additionally, knockdown of Cav-1 in MCF-7/G1P3 cells significantly reduced migratory capacity (p=.0005). Taken together, our results demonstrate a role for G1P3- induced mtROS in augmenting the expression of Cav1 to promote breast cancer cell migration.

Presented at the 2021 Student Creative Arts and Research Symposium