CD82 inhibits canonical Wnt signalling by controlling the cellular distribution             of β-catenin in carcinoma cells.
We have recently unravelled a novel function for CD82 in E-cadherin-mediated             cellular adhesion. CD82 inhibits β-catenin tyrosine phosphorylation and stabilizes             E-cadherin-β-catenin complexes at the cell membrane. This function inhibits cancer             cell dissociation from the primary cancer nest and limits metastasis. In this             study, we focused on the effect of CD82 on the Wnt/β-catenin (canonical) pathway,             which controls the cellular distribution of β-catenin. CD82 had no effect on the             expression of Wnt proteins but led to significant downregulation of Frizzled (Fzd)             2, 3, 5, 7 and 9, suggesting downregulation of the Wnt/β-catenin pathway. CD82             also inhibited phosphorylation of β-catenin at Ser45, Ser33, Ser37 and Thr41 by             downregulation of glycogen synthase kinase-3β (GSK-3β) and kinase casein kinase             1α (CK1α). Downregulation of GSK-3β and CK1α also led to accumulation of β-catenin             in the cytoplasm or at the cell membrane. CD82 translocated β-catenin to the cell             membrane, suggesting that CD82 strengthens the interaction between E-cadherin             and β-catenin. We concluded that CD82 attenuates Wnt signalling by controlling             β-catenin cellular distribution at multiple levels: i) inhibition of β-catenin             nuclear translocation by downregulation of Fzd receptor proteins; ii) accumulation             of β-catenin at the cell membrane by downregulation of GSK-3β and CK1α; and iii)             stabilization of the E-cadherin-β-catenin complex.
Division of Maxillofacial Diagnostic and Surgical Sciences, Department                     of Oral and Maxillofacial Surgery, Graduate School of Dental Science,                     Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Satomi
S
Chigita
Tsuyoshi
T
Sugiura
Masakazu
M
Abe
Yosuke
Y
Kobayashi
Miyuki
M
Shimoda
Megumi
M
Onoda
Kanemitsu
K
Shirasuna
D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D051157:Frizzled Receptors / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051861:Kangai-1 Protein / Q000378:metabolism*; D010766:Phosphorylation; D055550:Protein Stability; D021381:Protein Transport; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
D051157:Frizzled Receptors; D051861:Kangai-1 Protein; D051153:Wnt Proteins; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3