SWAP‐70 is important for invasive phenotypes of mouse embryo fibroblasts transformed by v‐Src

Abstract

SummarySWAP-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.2008 IUBMB IUBMB Life, 60(4): [236][237][238][239][240] 2008

SWAP70 Organizes the Actin Cytoskeleton and Is Essential for Phagocytosis

“…RAC1 activity is promoted by its binding to SWAP70 (Dwyer et al., 2015, Murugan et al., 2008, Shinohara et al., 2002, Sivalenka et al., 2008). RAC1 stimulates actin polymerization on phagosomes by Arp2/3 through activation of WAVE (Swanson, 2008).…”

“…SWAP70 is implicated in many diseases, including cancer (Chiyomaru et al., 2011, Fukui et al., 2007, Murugan et al., 2008, Shu et al., 2013), various autoimmune diseases (Bahaie et al., 2012, Biswas et al., 2012, Erdağ et al., 2012, Türkoğlu et al., 2014, Vural et al., 2009), and HIV (Kimbara et al., 2006). In this study, we show that SWAP70 is recruited to the surface of the nascent phagocytic cup in dendritic cells.…”

“…SWAP70 is expressed in many cell types, including mast cells (Gross et al., 2002), fibroblasts (Shinohara et al., 2002), dendritic cells (Oberbanscheidt et al., 2007), monocytes, and macrophages (Hilpelä et al., 2003). In these cells, the absence of SWAP70 leads to defects in actin polymerization and impairs cell migration, adhesion, polarization, and morphology (Bahaie et al., 2012, Chopin et al., 2010, Garbe et al., 2012, Murugan et al., 2008, Ocaña-Morgner et al., 2011, Pearce et al., 2006, Ripich and Jessberger, 2011, Shinohara et al., 2002, Sivalenka and Jessberger, 2004). SWAP70 can directly bind, bundle, and stabilize actin filaments by means of its C-terminal actin binding domain (Chacón-Martínez et al., 2013, Gomez-Cambronero, 2012, Hilpelä et al., 2003, Ihara et al., 2006, Murugan et al., 2008, Pearce et al., 2011, Shinohara et al., 2002).…”

“…In these cells, the absence of SWAP70 leads to defects in actin polymerization and impairs cell migration, adhesion, polarization, and morphology (Bahaie et al., 2012, Chopin et al., 2010, Garbe et al., 2012, Murugan et al., 2008, Ocaña-Morgner et al., 2011, Pearce et al., 2006, Ripich and Jessberger, 2011, Shinohara et al., 2002, Sivalenka and Jessberger, 2004). SWAP70 can directly bind, bundle, and stabilize actin filaments by means of its C-terminal actin binding domain (Chacón-Martínez et al., 2013, Gomez-Cambronero, 2012, Hilpelä et al., 2003, Ihara et al., 2006, Murugan et al., 2008, Pearce et al., 2011, Shinohara et al., 2002). SWAP70 regulates cellular actin dynamics and organization via activation of RHOA and RAC1 (Dwyer et al., 2015, Oberbanscheidt et al., 2007, Ocana-Morgner et al., 2009, Ocaña-Morgner et al., 2011, Shinohara et al., 2002, Sivalenka and Jessberger, 2004, Sivalenka et al., 2008).…”

“…SWAP70 regulates cellular actin dynamics and organization via activation of RHOA and RAC1 (Dwyer et al., 2015, Oberbanscheidt et al., 2007, Ocana-Morgner et al., 2009, Ocaña-Morgner et al., 2011, Shinohara et al., 2002, Sivalenka and Jessberger, 2004, Sivalenka et al., 2008). Binding of SWAP70 to phosphoinositides is required for this activation of RHO-GTPases (Murugan et al., 2008, Shinohara et al., 2002). We found that SWAP70 was transiently recruited to nascent phagosomes in human monocyte-derived dendritic cells.…”