Cell Biology

Cell-Cell Fusion

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Science  25 May 2012:
Vol. 336, Issue 6084, pp. 962
DOI: 10.1126/science.336.6084.962-a

Osteoclasts are cells that promote bone remodeling, and their hyperactivity is linked to bone-destructive disorders, including osteoporosis. Activated osteoclast precursors develop columnar actin structures, known as podosomes, which are similar to the invadopodia observed in invasive cancer cells. During osteoclast differentiation, cells can fuse with one another to create multinucleate cells. Oikawa et al. found that in osteoclastic cell cultures, a protein known to be involved in Src-induced cancer cell invadopodia production, Tks5, was also induced during osteoclastogenesis. Tyrosine phosphorylation of Tks5 by Src was required for the generation of circumferential podosomes in osteoclasts and for their fusion. Knockdown of Tks5 in osteoclasts interfered with circumferential podosome formation and cell–cell fusion, whereas polarized membrane extensions seemed to be unaffected. Tks5-expressing osteoclasts were also able to fuse with melanoma cells. Similar osteoclast–cancer cell hybrid cells have been detected in bone lesions in myeloma patients. Thus, Src-Tks5 signaling may represent a potential therapeutic target for the treatment of bone-destructive diseases and malignancies.

J. Cell Biol. 197, 553 (2012).

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