Figure 1.

Unraveling and targeting mechanisms of cancer cell fusion. (a) Tumor cells and mesenchymal stem cells (MSCs) are capable of spontaneous fusion, which is augmented with hypoxia; (b) Fusion in hypoxic conditions can be facilitated by the engagement of the exposed phosphatidyl serine (PtdSer) of apoptotic cells with PtdSer receptors (PtdSerR) on tumor cells or MSCs. Engagement of this type facilitates podosome formation that ultimately leads to robust activation of the F actin of the attacking fusion partner and MyoII of the receiving cell; (c) Green arrows indicate resisting forces from the actomyosin network, and black arrows indicate pushing forces from invasive protrusions of the attacking cell; (d) Hybrids formed in this way represent an accelerated evolution of sorts, sometimes giving rise to cells with enhanced metastatic potential or the ability to resist drug treatment. Inhibiting the engagement of apoptotic cells via PtdSer represents one potential therapeutic approach to the prevention of tumor cell fusion.