Tks5-dependent formation of circumferential podosomes/invadopodia mediates cell-cell fusion

Tsukasa Oikawa, Masaaki Oyama, Hiroko Kozuka-Hata, Shunsuke Uehara, Nobuyuki Udagawa, Hideyuki Saya, Koichi Matsuo

研究成果: Article査読

62 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)553-568
ページ数16
ジャーナルJournal of Cell Biology
197
4
DOI
出版ステータスPublished - 05-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • Cell Biology

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