STAP-2 Protein Expression in B16F10 Melanoma Cells Positively Regulates Protein Levels of Tyrosinase, Which Determines Organs to Infiltrate in the Body

J Biol Chem. 2015 Jul 10;290(28):17462-73. doi: 10.1074/jbc.M115.658575. Epub 2015 May 28.

Abstract

Melanoma is the most serious type of skin cancer, with a highly metastatic phenotype. In this report, we show that signal transducing adaptor protein 2 (STAP-2) is involved in cell migration, proliferation, and melanogenesis as well as chemokine receptor expression and tumorigenesis in B16F10 melanoma cells. This was evident in mice injected with STAP-2 shRNA (shSTAP-2)-expressing B16F10 cells, which infiltrated organs in a completely different pattern from the original cells, showing massive colonization in the liver, kidney, and neck but not in the lung. The most important finding was that STAP-2 expression determined tyrosinase protein content. STAP-2 colocalized with tyrosinase in lysosomes and protected tyrosinase from protein degradation. It is noteworthy that B16F10 cells with knocked down tyrosinase showed similar cell characteristics as shSTAP-2 cells. These results indicated that tyrosinase contributed to some cellular events beyond melanogenesis. Taken together, one possibility is that STAP-2 positively regulates the protein levels of tyrosinase, which determines tumor invasion via controlling chemokine receptor expression.

Keywords: adaptor protein; chemokine; melanoma; protein degradation; tumor metastasis; tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Shape
  • Cell Survival
  • Gene Knockdown Techniques
  • Lysosomes / metabolism
  • Melanins / metabolism
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / secondary
  • Mice
  • Mice, Inbred C57BL
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism*
  • Neoplasm Invasiveness
  • Organ Specificity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, Chemokine / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Melanins
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Small Interfering
  • Receptors, Chemokine
  • Recombinant Proteins
  • STAP2 protein, mouse
  • Monophenol Monooxygenase