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

细胞-细胞融合需要细胞质膜和细胞骨架的动态重排，这一过程涉及许多先前已知的因素。然而，细胞-细胞融合的机制和后果仍然不清楚。这项研究揭示了一种接头蛋白Tks5对于周状足小体的形成和破骨细胞融合都是必不可少的，而不改变破骨细胞的分化。由于已知Tks5可以促进癌细胞内侵足的形成，我测试了这些细胞是否也有与破骨细胞融合的潜力。在测试的细胞中，B16F0黑色素瘤细胞形成了具有Tks5积累的周向内凹。在炎症环境中，B16F0黑色素瘤细胞与破骨细胞共培养可促进黑色素瘤-破骨细胞杂交细胞的形成。这些结果揭示了一种以前未知的Tks5调节周向足质体/侵入足质体形成和细胞-细胞融合的机制。

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.