title: Cell surface localised Hsp70 is a cancer specific regulator of clathrin-independent endocytosis.
abstract: The stress inducible heat shock protein 70 (Hsp70) is present specifically on the tumour cell surface yet without a pro-tumour function revealed. We show here that cell surface localised Hsp70 (sHsp70) supports clathrin-independent endocytosis (CIE) in melanoma models. Remarkably, ability of Hsp70 to cluster on lipid rafts in vitro correlated with larger nano-domain sizes of sHsp70 in high sHsp70 expressing cell membranes. Interfering with Hsp70 oligomerisation impaired sHsp70-mediated facilitation of endocytosis. Altogether our findings suggest that a sub-fraction of sHsp70 co-localising with lipid rafts enhances CIE through oligomerisation and clustering. Targeting or utilising this tumour specific mechanism may represent an additional benefit for anti-cancer therapy.
authors.affiliation: Center for Advanced Bioanalysis GmbH, Linz, Austria.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Nimmervoll
authors.affiliation: Center for Advanced Bioanalysis GmbH, Linz, Austria; Institute for Biophysics, Johannes Kepler University, Linz, Austria.
authors.forename: Lilia A
authors.initials: LA
authors.lastname: Chtcheglova
authors.affiliation: Center for Advanced Bioanalysis GmbH, Linz, Austria.
authors.forename: Kata
authors.initials: K
authors.lastname: Juhasz
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nunilo
authors.initials: N
authors.lastname: Cremades
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Francesco A
authors.initials: FA
authors.lastname: Aprile
authors.affiliation: Center for Advanced Bioanalysis GmbH, Linz, Austria.
authors.forename: Alois
authors.initials: A
authors.lastname: Sonnleitner
authors.affiliation: Center for Advanced Bioanalysis GmbH, Linz, Austria; Institute for Biophysics, Johannes Kepler University, Linz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Hinterdorfer
authors.affiliation: Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Vigh
authors.affiliation: Center for Advanced Bioanalysis GmbH, Linz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Preiner
authors.affiliation: Center for Advanced Bioanalysis GmbH, Linz, Austria; Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: balogi.zsolt@koki.mta.hu.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Balogi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology*; D021962:Membrane Microdomains; D051379:Mice; D066329:Protein Aggregates
chemical_list: D002966:Clathrin; D018840:HSP70 Heat-Shock Proteins; D066329:Protein Aggregates
keywords: Cancer; Clustering; Endocytosis; Hsp70; Membrane