Table 1.
Proteins involved in invadopodial formation and activity
| Gene | Role in invadopodial life cycle | References |
|---|---|---|
| AFAP1 | Actin dynamics | (Dorfleutner et al., 2008) |
| ENAH/VASP** | Actin dynamics | (Hagedorn et al., 2014) |
| ARP2/3** | Actin dynamics | (Yamaguchi et al., 2005) |
| CARMIL2 | Actin dynamics | (Lanier et al., 2015) |
| CALD1 | Actin dynamics | (Mukhopadhyay et al., 2009) |
| CDC42** | Actin dynamics | (Lohmer et al., 2016; Nakahara et al., 2003) |
| ADF/CFL1** | Actin dynamics | (Hagedorn et al., 2014; Yamaguchi et al., 2005) |
| CRP2 | Actin dynamics | (Hoffmann et al., 2016) |
| DRF1-3 | Actin dynamics | (Lizarraga et al., 2009) |
| ERK | Actin dynamics | (Ayala et al., 2008) |
| ETAR | Actin dynamics | (Semprucci et al., 2015) |
| FSCN1 | Actin dynamics | (Vignjevic et al., 2006) |
| FLNA | Actin dynamics | (Takkunen et al., 2010) |
| GRB2 | Actin dynamics | (Oikawa et al., 2008) |
| HIF1A | Actin dynamics | (Md Hashim et al., 2013) |
| ITSN1/2 | Actin dynamics | (Gryaznova et al., 2015) |
| ARHGAP35 | Actin dynamics | (Bravo-Cordero et al., 2011; Nakahara et al., 1998) |
| ARHGEF28 | Actin dynamics | (Bravo-Cordero et al., 2011) |
| PODXL | Actin dynamics | (Lin et al., 2014) |
| RHOC | Actin dynamics | (Bravo-Cordero et al., 2011) |
| TRMP7 | Actin dynamics | (Visser et al., 2013) |
| VCL | Actin dynamics | (Branch et al., 2012) |
| WICH/WIRE | Actin dynamics | (Garcia et al., 2016) |
| ARHGEF7 | Actin dynamics | (Md Hashim et al., 2013) |
| ATX | Actin dynamics | (Harper et al., 2010) |
| EPAC | Actin dynamics | (Harper et al., 2010) |
| PIP5KIα | Actin dynamics | (Yamaguchi et al., 2010) |
| SVIL | Actin dynamics | (Crowley et al., 2009) |
| LAMTOR1 | Actin dynamics | (Hoshino et al., 2009) |
| FGD1 | Actin dynamics | (Ayala et al., 2009) |
| NCK1 | Actin dynamics, Matrix degradation | (Stylli et al., 2009; Yamaguchi et al., 2005) |
| ROCK1/2 | Actin dynamics, Matrix degradation | (Jerrell and Parekh, 2016; Vishnubhotla et al., 2007) |
| TLN1 | Actin dynamics, Matrix degradation | (Beaty et al., 2014; Mueller et al., 1992) |
| KISS1R | Actin dynamics, MMP activation | (Goertzen et al., 2016) |
| TIS21 | Actin dynamics, regulation of ROS | (Choi and Lim, 2013) |
| ARF6 | Cargo transport | (Hashimoto et al., 2004) |
| VAV1 | Cdc42 activation | (Razidlo et al., 2014) |
| β1 and β3 Integrin** | ECM attachment, actin dynamics | (Beaty et al., 2013; Hagedorn et al., 2009; Mueller and Chen, 1991) |
| HDAC6 | EGF signaling, hypoxic conditions | (Rey et al., 2011) |
| PXN | Erk activation | (Badowski et al., 2008; Bowden et al., 1999) |
| EXO70 | Exocyst complex, actin dynamics | (Liu et al., 2009) |
| SEC8 | Exocyst complex, actin dynamics | (Liu et al., 2009) |
| ACC1 | Fatty acid synthesis and de novo lipidogenesis | (Scott et al., 2012) |
| EGF | Induction | (Yamaguchi et al., 2005) |
| MET | Induction | (Rajadurai et al., 2012) |
| NTN1 | Induction | (Hagedorn et al., 2013) |
| PDGF | Induction | (Eckert et al., 2011) |
| ROS | Induction | (Diaz et al., 2009; Gianni et al., 2009) |
| SRC | Induction | (Chen, 1989) |
| TGF-β | Induction | (Eckert et al., 2011; Pignatelli et al., 2012) |
| RPS6KA1 | Induction, hypoxic conditions | (Lucien et al., 2011) |
| ORAI1 | Invadopodia assembly and Matrix degradation | (Sun et al., 2014) |
| STIM1 | Invadopodia assembly and Matrix degradation | (Sun et al., 2014) |
| PLEC | Invadopodia stabilization | (Sutoh Yoneyama et al., 2014) |
| PAK1 | Invadopodial disassembly | (Moshfegh et al., 2014) |
| VIM | Invadopodial elongation | (Schoumacher et al., 2010) |
| Microtubules | Invadopodial elongation | (Schoumacher et al., 2010) |
| IMP3 | Invadopodial formation, multiple mechanisms | (Hwang et al., 2012) |
| EZR | Invadopodial turnover | (Hoskin et al., 2015) |
| RAC1** | Invadopodial turnover | (Moshfegh et al., 2014; Nakahara et al., 2003; Ziel et al., 2009) |
| DPP4 | Matrix degradation | (Chen and Kelly, 2003) |
| HIC-5 | Matrix degradation | (Pignatelli et al., 2012) |
| MMP2 | Matrix degradation | (Deryugina et al., 2002) |
| MMP9 | Matrix degradation | (Nascimento et al., 2010) |
| MT1-MMP (MMP14) | Matrix degradation | (Nakahara et al., 1997; van Hinsbergh et al., 2006) |
| NEDD9 | Matrix degradation | (McLaughlin et al., 2014) |
| NHE-1 | Matrix degradation | (Busco et al., 2010) |
| PRKD1 | Matrix degradation | (Bowden et al., 1999) |
| TWIST1 | Matrix degradation | (Eckert et al., 2011) |
| uPAR | Matrix degradation | (Furmaniak-Kazmierczak et al., 2007) |
| NOX1 | Matrix degradation | (Gianni et al., 2010b) |
| PI3K3CA | Matrix degradation | (Nakahara et al., 2003; Yamaguchi et al., 2011) |
| FAP | Matrix degradation, Protease docking, localization | (Chen, 1996; Monsky et al., 1994) |
| PFN1 | Membrane composition | (Valenzuela-Iglesias et al., 2015) |
| GDI1 | Membrane trafficking | (Lohmer et al., 2016) |
| GAB1 | Met signaling | (Rajadurai et al., 2012) |
| RAB40B | MMP trafficking | (Jacob et al., 2013) |
| WIP | MMP trafficking, actin dynamics | (Garcia et al., 2012) |
| CD44 | MT1-MMP recruitment | (Vikesaa et al., 2006; Zhao et al., 2016) |
| JIP3/4 | MT1-MMP trafficking | (Marchesin et al., 2015) |
| CD147 | MT1-MMP trafficking | (Grass et al., 2012) |
| CDCP1 | MT1-MMP trafficking | (Miyazawa et al., 2013) |
| IQGAP1 | MT1-MMP trafficking | (Sakurai-Yageta et al., 2008) |
| RAB8A | MT1-MMP trafficking | (Bravo-Cordero et al., 2007) |
| RHOA | MT1-MMP trafficking | (Bravo-Cordero et al., 2011) |
| STX4 | MT1-MMP trafficking | (Williams et al., 2014) |
| VAMP7 | MT1-MMP trafficking | (Steffen et al., 2008; Williams et al., 2014) |
| ZF21 | MT1-MMP trafficking | (Hoshino et al., 2013b) |
| YB-1 | MT1-MMP trafficking | (Lovett et al., 2010) |
| KIF3A/B | MT1-MMP trafficking | (Wiesner et al., 2010) |
| KIF5A | MT1-MMP trafficking | (Wiesner et al., 2010) |
| TOM1L1 | MT1-MMP trafficking | (Chevalier et al., 2016) |
| N-WASP** | MT1-MMP trafficking, actin dynamics | (Lorenz et al., 2004; Yamaguchi et al., 2005) |
| CTTN | MT1-MMP trafficking, actin dynamics | (Artym et al., 2006; Bowden et al., 1999; Clark et al., 2007) |
| CLIC3 | MT1-MMP trafficking, cargo selection | (Macpherson et al., 2014) |
| ABL1/2 | MT1-MMP trafficking, EGF signaling | (Beaty et al., 2013; Smith-Pearson et al., 2010; Sun et al., 2009) |
| SNAP23 | MT1-MMP trafficking, Src and EGFR trafficking | (Williams and Coppolino, 2014; Williams et al., 2014) |
| TKS4/5 | MT1-MMP trafficking, Src signaling | (Abram et al., 2003) |
| SYNJ2 | RAC1 activity | (Chuang et al., 2004) |
| SHIP2 | Regulates invadopodia PI(3,4)P2 levels | (Sharma et al., 2013) |
| PDPN | Regulator of Invadopodia maturation | (Martin-Villar et al., 2015) |
| RALB/RALBP1 | Required, unknown mechanism | (Neel et al., 2012) |
| PLS1 | Required, unknown mechanism | (Schoumacher et al., 2010) |
| FAK | Src signaling | (Hauck et al., 2002; Vitale et al., 2008) |
| P130CAS | Src signaling | (Alexander et al., 2008) |
| TP53 | Src signaling | (Mukhopadhyay et al., 2009) |
| ASAP1 | Src signaling | (Bharti et al., 2007) |
| ADRB2 | Src signaling | (Creed et al., 2015) |
| CAPN2 | Src signaling | (Cortesio et al., 2008) |
| ERK1/2 | Src signaling | (Furmaniak-Kazmierczak et al., 2007) |
| PTP1B | Src signaling | (Cortesio et al., 2008) |
| NOXA1 | Src signaling | (Gianni et al., 2010a) |
| Laminin-332 | Src signaling | (Liu et al., 2010) |
| Gαi2 | Src trafficking to invadopodia | (Ward et al., 2015) |
| STX12 | Src, EGF trafficking | (Williams and Coppolino, 2014) |
| ADAM12 | Src/EGF signaling, hypoxic conditions | (Albrechtsen et al., 2011) |
| TGM1/2 | TGF-β signaling | (Lauzier et al., 2012) |
| CAV-1 | Vesicle / membrane trafficking | (Caldieri et al., 2009; Yamaguchi et al., 2009) |
| DNM2 | Vesicle trafficking | (Baldassarre et al., 2003) |
| FBP17 | Vesicle trafficking | (Yamamoto et al., 2011) |
| WASH | Vesicle trafficking | (Monteiro et al., 2013) |
| RAB4 | Vesicle trafficking | (Frittoli et al., 2014) |
| RAB5A | Vesicle trafficking | (Frittoli et al., 2014) |
The proteins listed were identified in numerous cancer cell types and model systems. Rows shaded grey represent proteins with direct roles in invadopodial membrane formation and function.
**
Identified in numerous species, indicating a conserved mechanism.