CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma

Oncotarget. 2016 Oct 4;7(40):64778-64784. doi: 10.18632/oncotarget.11415.

Abstract

Melanoma is a very malignant disease and there are still no effective treatments. CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth. However, the function of CD147 and GLUT-1 in melanoma have not been completely understood. Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue. In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells. Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199. Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells. In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT. Our results could help validate CD147 as a new therapeutic target for treating melanoma.

Keywords: CD147; GLUT-1; PI3K/Akt pathway; glycolysis; melanoma.

MeSH terms

  • Animals
  • Basigin / genetics
  • Basigin / metabolism*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Excitatory Amino Acid Transporter 2 / genetics
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucose / metabolism*
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / therapy
  • Mice
  • Mice, Nude
  • Nevus / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • Excitatory Amino Acid Transporter 2
  • RNA, Small Interfering
  • Basigin
  • Phosphatidylinositol 3-Kinases
  • Glucose

Supplementary concepts

  • Epidermal Nevus