Cell　fusion　plays　a　crucial　role　in　cancer　progression　and　leads　to　massive　aberrant　changes　in　chromosome　and　gene　expression　involved　in　tumor　metastasis.　Cancer　cells　can　fuse　with　many　cell　types,　including　stromal　cells,　epithelial　cells,　macrophages,　and　endothelial　cells.　Mesenchymal　stem　cells　(MSCs)　have　been　reported　to　migrate　and　incorporate　into　tumor　sites　during　cancer　progression.　However,　the　underlying　mechanism　of　stem　cell　fusion　in　tumor　metastasis　has　not　been　fully　deciphered.　In　this　research,　we　established　a　cell　fusion　model　between　lung　cancer　cells　and　MSCs　in　vitro.　We　found　that　the　hybrid　cells　showed　enhanced　metastatic　capacity　with　increased　expression　of　MMP-2　and　MMP-9,　whereas　the　proliferation　ability　was　inhibited　and　cell　cycle　was　blocked　in　the　G(0)/G(1)　phase　with　elevated　expression　of　p21,　p27,　and　p53.　Moreover,　the　hybrid　cells　lost　epithelial　morphology　and　exhibited　an　epithelial-mesenchymal　transition　(EMT)　change　with　downregulation　of　E-cadherin　and　upregulation　of　N-cadherin,　Vimentin,　-SMA　and　Fibronectin1.　Meanwhile,　the　expressions　of　EMT　transcription　factors,　including　Snail1,　Slug,　Twist1,　Zeb1,　and　Zeb2,　were　also　increased　in　hybrid　cells.　More　important,　the　fusion　hybrids　acquired　stem　cell-like　properties,　which　exhibited　increased　expression　stem　cell　transcription　factors　Oct4,　Sox2,　Nanog,　Kif4　as　well　as　Bmi1.　Taken　together,　our　results　suggested　that　cell　fusion　between　lung　cancer　cells　and　MSCs　offered　enhanced　metastatic　capacity　and　characteristics　of　cancer　stem　cell　by　undergoing　EMT.　This　study　will　contribute　to　explaning　the　origin　of　lung　cancer　stem　cells　and　to　elucidate　the　role　of　cell　fusion　in　cancer　metastasis.