Cell　fusion　is　a　highly　regulated　process　involved　in　cancer　development,　tissue　regeneration　and　other　physiological　and　pathological　events.　Many　studies　have　shown　that　cancer　cells　can　fuse　with　different　types　of　cells　such　as　mesenchymal　stem　cells　(MSCs)　and　macrophages,　which　are　behaved　as　two　important　fusogenic　candidates　in　the　tumor　microenvironment.　However,　the　underlying　mechanisms　of　cell　fusion　between　macrophages　and　malignant　cells　in　cancer　progression　has　not　been　fully　clarified.　The　aim　of　the　present　study　was　to　investigate　the　effects　and　mechanisms　of　cell　fusion　between　macrophages　and　breast　cancer　cells　on　tumorigenesis　and　metastasis.　Our　results　indicated　that　the　hybrids　exhibited　enhanced　proliferation,　colony　formation,　migration　and　invasion　capabilities,　as　well　as　suppressed　apoptosis　compared　with　parental　breast　cancer　cells.　Moreover,　the　hybrid　cells　displayed　EMT　with　a　significant　downregulation　of　E-cadherin　and　upregulation　of　N-cadherin,　Vimentin　and　Snail,　as　well　as　an　obviously　increased　expression　of　MMP-2,　MMP-9,　uPA　and　S100A4.　Mechanistically,　we　found　that　the　TCF/LEF　transcription　factor　activity　of　Wnt/beta-catenin　pathway　and　the　expression　of　its　downstream　target　genes　including　cyclin　D1　and　c-Myc　were　increased　in　the　hybrid　cells.　Furthermore,　our　data　confirmed　that　the　promoting　effects　of　fusion　of　macrophages　on　breast　cancer　cell　proliferation,　migration　and　invasion　could　be　blocked　by　treatment　with　XAV-939,　a　Wnt/beta-catenin　signaling　pathway　inhibitor.　In　conclusion,　our　findings　demonstrate　that　fusion　of　macrophages　promotes　proliferation,　migration　and　invasion　of　breast　cancer　cells　through　activating　EMT　and　Wnt/beta-catenin　signaling　pathway.　Our　current　study　will　further　contribute　to　elucidate　the　mechanism　of　cell　fusion　in　tumorigenesis　and　metastasis,　and　to　develop　a　new　therapeutic　strategy　for　breast　cancer　treatment.