Abstract: In order to reveal the molecular mechanisms between cell fusion and tumor metastasis, we had successfully conducted a fusion model between breast cancer cells and macrophages. Previous studies found that the fusion hybrids exhibited significantly enhancing proliferation and metastasis abilities.Therefore, we next focused on the effects of cell fusion between breast cancer cells and macrophages on PI3K/AKT and MAPK/ERK signaling pathways closely related to tumor cell proliferation and metastasis. Western Blot results showed that the expression of the key marker proteins of PI3K/AKT and MAPK/ERK signaling pathways including p-PI3K, p-AKT and p-ERK1/2 was significantly up-regulated in the fused cells. After PI3K/AKT and MAPK/ERK signaling pathways being blocked by LY294002 and PD98059 inhibitors, the expression of p-AKT and p-ERK1/2 in the fused cells was obviously reduced, and the proliferation, migration and invasion abilities of the fused cells were inhibited. These results suggested that cell fusion between breast cancer cells and macrophages might promote the proliferation and metastasis of breast cancer by activating PI3K/AKT and MAPK/ERK signaling pathways. Our data also could provide new ideas for further understanding the mechanisms of cell fusion in tumorigenesis and metastasis.

Key words: cell fusion, breast cancer, macrophages, PI3K/AKT, MAPK/ERK