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

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)553-568
Number of pages16
JournalJournal of Cell Biology
Volume197
Issue number4
DOIs
Publication statusPublished - 2012 May 1

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ASJC Scopus subject areas

  • Cell Biology

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