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Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell–cell fusion
| Content Provider | Scilit |
|---|---|
| Author | Oikawa, Tsukasa Oyama, Masaaki Kozuka-Hata, Hiroko Uehara, Shunsuke Udagawa, Nobuyuki Saya, Hideyuki Matsuo, Koichi |
| Copyright Year | 2012 |
| Description | Osteoclasts fuse to form multinucleated cells during osteoclastogenesis. This process is mediated by dynamic rearrangement of the plasma membrane and cytoskeleton, and it requires numerous factors, many of which have been identified. The underlying mechanism remains obscure, however. In this paper, we show that Tks5, a master regulator of invadopodia in cancer cells, is crucial for osteoclast fusion downstream of phosphoinositide 3-kinase and Src. Expression of Tks5 was induced during osteoclastogenesis, and prevention of this induction impaired both the formation of circumferential podosomes and osteoclast fusion without affecting cell differentiation. Tyrosine phosphorylation of Tks5 was attenuated in Src−/− osteoclasts, likely accounting for defects in podosome organization and multinucleation in these cells. Circumferential invadopodia formation in B16F0 melanoma cells was also accompanied by Tks5 phosphorylation. Co-culture of B16F0 cells with osteoclasts in an inflammatory milieu promoted the formation of melanoma–osteoclast hybrid cells. Our results thus reveal an unexpected link between circumferential podosome/invadopodium formation and cell–cell fusion in and beyond osteoclasts. |
| Related Links | https://rupress.org/jcb/article-pdf/197/4/553/703312/jcb_201111116.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352951/pdf |
| Ending Page | 568 |
| Page Count | 16 |
| Starting Page | 553 |
| DOI | 10.1083/jcb.201111116 |
| Journal | Journal of Cell Biology |
| Issue Number | 4 |
| Volume Number | 197 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2012-05-14 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Phosphorylation Tks5 Circumferential Osteoclasts Osteoclast Fusion Melanoma Podosome B16f0 Mediated Journal: Journal of Cell Biology (Vol- 197, Issue- 4) |
| Content Type | Text |