Protein phosphatase activity of PTEN inhibited the invasion of glioma cells with epidermal growth factor receptor mutation type III expression.
PTEN is a major tumor suppressor gene that has been shown to inhibit cell invasion. Its mutation has been found in 20-40% of malignant gliomas. Meanwhile, the type III EGFR mutation (EGFRvIII), which was frequently found in gliomas, promoted cell invasion. In the present study, the effects of PTEN on cell invasion were investigated in U87DeltaEGFR glioblastoma cells with EGFRvIII expression but missing PTEN. The cell invasion was downregulated by transfection of phosphatase-active forms of PTEN (wild-type and G129E) but not by PTEN (C124A) with an inactive phosphatase domain; the effects were correlated with decreased tyrosine phosphatase levels of FAK at Tyr397, which was increased by EGFRvIII. Overexpression of FAK mutant (Y397F) could partially mimic the effect of PTEN on cell invasion. Although EGFRvIII increased the levels of P-Akt and PTEN eliminated it, PI-3K inhibitors, wortmannin or Ly294002, could not decrease the cell invasion. In conclusion, PTEN could inhibit cell invasion even in the presence of the constitutively active EGFR; this inhibition depended on its protein phosphatase activity, partially by dephosphorylating FAK, but not depended on its lipid phosphatase activity.
Cai
Xiu-Mei
XM
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Tao
Bei-Bei
BB
Wang
Li-Ying
LY
Liang
Yu-Long
YL
Jin
Jia-Wei
JW
Yang
Yong
Y
Hu
Ya-Li
YL
Zha
Xi-Liang
XL
D045744:Cell Line, Tumor; D002465:Cell Movement; D066246:ErbB Receptors / Q000235:genetics* / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005909:Glioblastoma; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000517:prevention & control*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing
D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011506:Proteins; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051059:PTEN Phosphohydrolase