FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis

Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10374-9. doi: 10.1073/pnas.181222898. Epub 2001 Aug 14.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle / genetics
  • Cell Division / genetics
  • Chromosomes, Human, Pair 8 / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • Male
  • Microtubules / metabolism
  • Mitosis / genetics
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Nerve Tissue Proteins
  • Peptide Elongation Factor 1 / metabolism
  • Phosphorylation
  • Protein Binding
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • FEZ1 protein, human
  • LZTS1 protein, human
  • Nerve Tissue Proteins
  • Peptide Elongation Factor 1
  • Tumor Suppressor Proteins
  • CDC2 Protein Kinase