Natural bioactive molecules induce a reduction of surface alpha-enolase in breast cancer cells

Cell surface expression of alpha-enolase, a glycolytic enzyme displaying moonlighting activities, has been shown to contribute to cancer cell invasion and metastasis formation. Although the functional role of surface alpha-enolase in cancer spreading has been clearly linked to the protein non-enzymatic function of binding plasminogen and enhancing plasmin formation, the cellular pathways underlying cell surface transport remain largely elusive. We have previously demonstrated that pro-invasive stimuli promote the surface expression of alpha-enolase in breast cancer cells. To further investigate alpha-enolase translocation to the plasma membrane and to identify the signaling involved in this process, we stimulated breast cancer cells with curcumin, berberine, resveratrol and other natural bioactive molecules known to counteract cell migration and invasion. We observed that the induced decrease in cell motility correlates with a reduced level of alpha-enolase on the plasma membrane, consistent with surface enolase activity. Furthermore, with the aim to explore if these bioactive molecules have straight interaction with alpha-enolase, we carried out in silico analysis by means of Induced Fit Docking. Our results may contribute to shedding light on the control of surface expression of alpha-enolase in cancer cells and suggest novel targets to counteract the metastatic potential of tumors.