A new role of podosome formation as a mediator of cell-cell fusion

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Cell-cell fusion requires dynamic rearrangement of the plasma membrane and cytoskeleton, and this process involves numerous previously characterized factors. However, the mechanisms and consequences of cell-cell fusion remains obscure. This study revealed that an adaptor protein Tks5 is essential for both formation of circumferential podosomes and osteoclast fusion without altering osteoclast differentiation. As Tks5 is known to promote the formation of invadopodia in cancer cells, I tested if these cells also have the potential to fuse with osteoclasts. Among the cells tested, B16F0 melanoma cells formed circumferential invadopodia with Tks5 accumulation. Co-culture of B16F0 melanoma cells with osteoclasts in an inflammatory milieu promoted increased formation of melanoma-osteoclast hybrid cells. These results revealed a previously unknown mechanism of regulation of both circumferential podosomes/invadopodia formation and cell-cell fusion by Tks5.