Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1

Curr Biol. 2000 Aug 24;10(16):1009-12. doi: 10.1016/s0960-9822(00)00652-7.

Abstract

The 'metastasis suppressor' CD82/KAI-1, a member of the tetraspanin superfamily of transmembrane proteins, is widely distributed in normal tissues [1], and has been shown to be suppressed in the advanced stages of various epithelial malignancies [2-6]. Although the physiological relevance of this change is unknown, in vitro data show that ectopically expressed CD82/KAI-1 can suppress tumor cell migration, a process underlying the dissemination of tumor cells in vivo [5]. The function of CD82/KAI-1 is not known and it has been proposed that association of CD82/KAI-1 with other cell-surface proteins may be pivotal in directing its biological activities [7,8]. We show here that the CD82/KAI-1 tetraspanin is directly associated with the EGF receptor (EGFR), and that ectopic expression of CD82/KAI-1 in epithelial cells specifically suppresses EGF-induced lamellipodial extensions and cell migration. In cells expressing CD82/KAI-1, the initial activation of EGFR is not affected, but subsequent desensitization of EGF-induced signaling occurs more rapidly. This attenuation is correlated with an increased rate of receptor endocytosis. These results identify CD82/KAI-1 as a new regulator of EGF-induced signaling and show that the association of EGFR with the tetraspanin is critical in EGFR desensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Cell Line
  • Epithelial Cells / metabolism
  • ErbB Receptors / metabolism*
  • Gene Expression Regulation
  • Humans
  • Kangai-1 Protein
  • Membrane Glycoproteins / metabolism*
  • Proto-Oncogene Proteins*
  • Signal Transduction*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • CD82 protein, human
  • Kangai-1 Protein
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • ErbB Receptors