FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis.
The FEZ1/LZTS1 gene maps to chromosome 8p22, a region that is frequently deleted in human tumors. Alterations in FEZ1/LZTS1 expression have been observed in esophageal, breast, and prostate cancers. Here, we show that introduction of FEZ1/LZTS1 into Fez1/Lzts1-negative cancer cells results in suppression of tumorigenicity and reduced cell growth with accumulation of cells at late S-G(2)/M stage of the cell cycle. Fez1/Lzts1 protein is hyperphosphorylated by cAMP-dependent kinase during cell-cycle progression. We found that Fez1/Lzts1 is associated with microtubule components and interacts with p34(cdc2) at late S-G(2)/M stage in vivo. Present data show that FEZ1/LZTS1 inhibits cancer cell growth through regulation of mitosis, and that its alterations result in abnormal cell growth.
Ishii
H
H
Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107-5799, USA.
Vecchione
A
A
Murakumo
Y
Y
Baldassarre
G
G
Numata
S
S
Trapasso
F
F
Alder
H
H
Baffa
R
R
Croce
C M
CM
D048868:Adaptor Proteins, Signal Transducing; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins; D020648:Peptide Elongation Factor 1 / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C528597:FEZ1 protein, human; C118711:LZTS1 protein, human; D009419:Nerve Tissue Proteins; D020648:Peptide Elongation Factor 1; D025521:Tumor Suppressor Proteins; D016203:CDC2 Protein Kinase