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

H Ishii1, A Vecchione, Y Murakumo

  • 1Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107-5799, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 16, 2001
PubMed

Insights

The FEZ1/LZTS1 gene suppresses tumor growth by regulating mitosis. Loss of FEZ1/LZTS1 (also known as tumor suppressor FEZ1/LZTS1) leads to abnormal cell growth and accumulation in cancer cells.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • The FEZ1/LZTS1 gene is located on chromosome 8p22, a region frequently deleted in human tumors.
  • Altered FEZ1/LZTS1 expression is implicated in esophageal, breast, and prostate cancers.

Purpose of the Study:

  • To investigate the role of FEZ1/LZTS1 in cancer cell growth and tumorigenicity.
  • To elucidate the mechanism by which FEZ1/LZTS1 regulates the cell cycle and mitosis.

Main Methods:

  • Introduction of FEZ1/LZTS1 into cancer cells lacking the gene.
  • Cell cycle analysis to observe cell accumulation.
  • Western blotting and co-immunoprecipitation to study protein interactions and phosphorylation status.

Main Results:

  • Restoration of FEZ1/LZTS1 suppressed tumor formation and reduced cancer cell proliferation.
  • FEZ1/LZTS1-expressing cells accumulated at the late S-G(2)/M phase of the cell cycle.
  • Fez1/Lzts1 protein is hyperphosphorylated by cAMP-dependent kinase and interacts with microtubule components and p34(cdc2) during mitosis.

Conclusions:

  • FEZ1/LZTS1 acts as a tumor suppressor by inhibiting cancer cell growth through the regulation of mitosis.
  • Alterations in FEZ1/LZTS1 contribute to abnormal cell growth and tumorigenesis.

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