SWAP-70 is important for invasive phenotypes of mouse embryo fibroblasts transformed by v-Src
Avaniyapuram Kannan Murugan1, Sayoko Ihara, Emi Tokuda
1Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract:
SWAP-70 is a protein involved in actin rearrangement, especially in membrane ruffling. Mouse embryo fibroblasts (MEFs) deficient in SWAP-70 show impaired membrane ruffling and fail to grow in soft agar after transformation by v-Src. Here, we show that v-Src transformed MEFs expressing SWAP-70 are highly invasive. MEFs expressing SWAP-70 or v-Src alone were far less invasive, suggesting that both proteins were required for the cells to be invasive. Expression of both SWAP-70 and v-Src induced constant membrane ruffling, which may cause vigorous cell movement, probably required for invasiveness of the cells. Expression of v-Src alone morphologically transformed MEFs but formed lamellipodia rather than membrane ruffles, suggesting less aggressive nature of the cells compared with those expressing both SWAP-70 and v-Src. These results suggest that v-Src and SWAP-70 act synergistically in the invasion activity of MEFs.
Insights
SWAP-70 protein and v-Src oncogene synergize to enhance cancer cell invasion. Together, they induce constant membrane ruffling, promoting vigorous cell movement and invasiveness in mouse embryo fibroblasts.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- SWAP-70 is a key regulator of actin cytoskeleton dynamics, particularly membrane ruffling.
- Mouse embryo fibroblasts (MEFs) lacking SWAP-70 exhibit defective membrane ruffling and anchorage-independent growth post-v-Src transformation.
- The oncogenic protein v-Src drives cellular transformation and influences cell motility.
Purpose of the Study:
- To investigate the synergistic role of SWAP-70 and v-Src in the invasive potential of MEFs.
- To elucidate the mechanisms by which SWAP-70 and v-Src cooperate to promote cell invasion.
Main Methods:
- Generation and characterization of v-Src transformed MEFs with varying SWAP-70 expression levels.
- Assessment of cell invasion using soft agar assays and in vitro invasion models.
- Microscopic analysis of cell morphology, membrane ruffling, and lamellipodia formation.
Main Results:
- MEFs co-expressing SWAP-70 and v-Src demonstrated significantly enhanced invasiveness compared to cells expressing either protein alone.
- Simultaneous expression of SWAP-70 and v-Src induced persistent membrane ruffling and vigorous cell movement.
- v-Src expression alone led to morphological transformation and lamellipodia formation, but not the high invasiveness observed with co-expression.
Conclusions:
- SWAP-70 and v-Src act synergistically to promote MEF invasiveness.
- Constant membrane ruffling induced by the combined action of SWAP-70 and v-Src is a critical factor for enhanced cell motility and invasion.
- This synergistic interaction highlights a novel mechanism contributing to the aggressive phenotype of certain cancer cells.
