TP53I11 Suppresses Extracellular Matrix-independent Survival and Mesenchymal Transition in Mammary Epithelial Cells

Extracellular matrix (ECM)-independent survival is an essential prerequisite for tumor metastasis and a hallmark of epithelial cancer stem cells and epithelial-mesenchymal transition (EMT). We found that, in MCF10A and MDA-MB-231 cells, loss of TP53I11 (Tumor Protein P53 Inducible Protein 11) enhanced the ECM-independent survival and suppressed glucose starvation induced cell death by increasing the activation of AMPK that confer cells metabolic flexibility to survive under stress conditions. We show here that, TP53I11 enhanced glycolysis and promoted proliferation of MCF10A and MDA-MB-231 cells in normal culture, but exerted negative effect on EMT, cell migration and invasion, and its overexpression suppressed tumor progression and metastasis of MDA-MB-231 cells in vivo. Considering cancer cells also are confronted with the hostile environment such as nutrient scarcity during tumorigenesis and metastasis, our findings suggested that the disruption of metabolic flexibility by TP53I11 through inhibiting AMPK activation resulted in the suppression of tumorigenesis and metastasis of breast cancer.