title: A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells.
abstract: One of the hallmarks of cancer is the ability of tumor cells to invade surrounding tissues and metastasize. During metastasis, cancer cells degrade the extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. The formation of invadopodia is regulated by Rho GTPases, a family of proteins that regulates the actin cytoskeleton. Here, we describe a novel role for RhoG in the regulation of invadopodia disassembly in human breast cancer cells. Our results show that RhoG and Rac1 have independent and opposite roles in the regulation of invadopodia dynamics. We also show that SGEF (also known as ARHGEF26) is the exchange factor responsible for the activation of RhoG during invadopodia disassembly. When the expression of either RhoG or SGEF is silenced, invadopodia are more stable and have a longer lifetime than in control cells. Our findings also demonstrate that RhoG and SGEF modulate the phosphorylation of paxillin, which plays a key role during invadopodia disassembly. In summary, we have identified a novel signaling pathway involving SGEF, RhoG and paxillin phosphorylation, which functions in the regulation of invadopodia disassembly in breast cancer cells.
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Silvia M
authors.identifier: 0000-0003-1107-389X
authors.initials: SM
authors.lastname: Goicoechea
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Ashtyn
authors.initials: A
authors.lastname: Zinn
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Sahezeel S
authors.initials: SS
authors.lastname: Awadia
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Snyder
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA rafael.garciamata@utoledo.edu.
authors.forename: Rafael
authors.identifier: 0000-0002-7116-4411
authors.initials: R
authors.lastname: Garcia-Mata
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D000069261:Podosomes / Q000378:metabolism*; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C473930:ARHGEF26 protein, human; D020662:Guanine Nucleotide Exchange Factors; C075397:RHOG protein, human; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins
keywords: Guanine-nucleotide exchange factors; Invadopodia; Paxillin; Rac1; RhoG; SGEF; Src