Cell surface localised Hsp70 is a cancer specific regulator of clathrin-independent endocytosis

FEBS Lett. 2015 Sep 14;589(19 Pt B):2747-53. doi: 10.1016/j.febslet.2015.07.037. Epub 2015 Aug 6.

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.

Keywords: Cancer; Clustering; Endocytosis; Hsp70; Membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Clathrin / metabolism*
  • Endocytosis*
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / metabolism*
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology*
  • Membrane Microdomains
  • Mice
  • Protein Aggregates

Substances

  • Clathrin
  • HSP70 Heat-Shock Proteins
  • Protein Aggregates