Regulation of c-Met signaling by the tetraspanin KAI-1/CD82 affects cancer cell migration

Miho Takahashi, Tsuyoshi Sugiura, Masakazu Abe, kotaro ishii, Kanemitsu Shirasuna

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

It has been proposed that the metastasis suppressor CD82/KAI-1, which is a member of the tetraspanin superfamily, regulates biological activity by associating with cell surface receptors or proteins. We show a novel association between CD82 and the hepatocyte growth factor (HGF) receptor c-Met. Although ectopic expression of CD82 in nonsmall cell lung carcinoma cells did not affect the tyrosine phosphorylation of c-Met, these cells showed significant suppression of HGF-induced lamellipodial protrusion and cell migration. CD82 selectively attenuated c-Met signaling via the Ras-Cdc42/Rac and the phosphatidylinositol 3-kinase/Cdc42/Rac pathways. In contrast, another c-Met signaling pathway that involves phosphatidylinositol 3-kinase/Akt and phosphatidylinositol 3-kinase/mitogen activated protein kinase was not affected by CD82. Signaling adapter proteins for c-Met, such as Grb2 and p85, exhibited reduced association with c-Met in cells that ectopically expressed CD82. These results indicate that the CD82-c-Met complex inhibits HGF-induced cancer cell migration by the inactivation of small GTP-binding proteins of the Rho family via c-Met adapter proteins.

Original languageEnglish
Pages (from-to)1919-1929
Number of pages11
JournalInternational Journal of Cancer
Volume121
Issue number9
DOIs
Publication statusPublished - Nov 1 2007

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Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-met
Cell Movement
Hepatocyte Growth Factor
Neoplasms
rho GTP-Binding Proteins
Cell Surface Receptors
Mitogen-Activated Protein Kinases
Tyrosine
Membrane Proteins
Phosphorylation
Neoplasm Metastasis
Carcinoma
Lung

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Regulation of c-Met signaling by the tetraspanin KAI-1/CD82 affects cancer cell migration. / Takahashi, Miho; Sugiura, Tsuyoshi; Abe, Masakazu; ishii, kotaro; Shirasuna, Kanemitsu.

In: International Journal of Cancer, Vol. 121, No. 9, 01.11.2007, p. 1919-1929.

Research output: Contribution to journalArticle

Takahashi, Miho ; Sugiura, Tsuyoshi ; Abe, Masakazu ; ishii, kotaro ; Shirasuna, Kanemitsu. / Regulation of c-Met signaling by the tetraspanin KAI-1/CD82 affects cancer cell migration. In: International Journal of Cancer. 2007 ; Vol. 121, No. 9. pp. 1919-1929.
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