title: Knockdown of Hop downregulates RhoC expression, and decreases pseudopodia formation and migration in cancer cell lines.
abstract: The Hsp90/Hsp70 organising protein (Hop) is a co-chaperone that mediates the interaction of Hsp90 and Hsp70 molecular chaperones during assembly of Hsp90 complexes in cells. Formation of Hsp90 complexes is a key intermediate step in the maturation and homeostasis of oncoproteins and several hormone receptors. In this paper, we demonstrate that knockdown of Hop decreased migration of Hs578T and MDA-MB-231 breast cancer cells. Hop was identified in isolated pseudopodia fractions; it colocalised with actin in lamellipodia, and co-sedimented with purified actin in vitro. Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms.
authors.affiliation: Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, University Road, Grahamstown 6140, South Africa.
authors.forename: Tarryn
authors.initials: T
authors.lastname: Willmer
authors.forename: Lara
authors.initials: L
authors.lastname: Contu
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Edkins
mesh_terms: D000199:Actins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D011554:Pseudopodia / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D000199:Actins; C476884:HOPX protein, human; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein