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Published on: July 17, 2020

Phosphatase activity of nuclear PTEN is required for CDX2-mediated intestinal differentiation of gastric carcinoma

Shuho Semba1, Shinya Satake, Mai Matsushita

  • 1Division of Pathology, Department of Pathology and Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. semba@med.kobe-u.ac.jp

Cancer Letters
|November 11, 2008
PubMed

Insights

Nuclear PTEN (phosphatase and tensin homolog) promotes intestinal differentiation in gastric cancer. This finding suggests nuclear PTEN localization is key for determining the intestinal phenotype in gastric carcinomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The PTEN tumor suppressor primarily functions in the cytoplasm, regulating the phosphatidylinositol 3-kinase-AKT pathway.
  • The role of nuclear PTEN in gastric carcinoma (GC) pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the biological significance of nuclear PTEN localization in gastric carcinoma.
  • To determine if nuclear PTEN influences the differentiation phenotype of GC cells.

Main Methods:

  • Transduction of recombinant PTEN and a phosphatase-dead mutant (G129E) into GC-derived TMK-1 cells.
  • Analysis of mRNA levels for CDX2 and intestinal claudins (CLDN3, CLDN4).
  • Examination of PTEN expression and claudin phenotype in GC tissue samples.

Main Results:

  • Recombinant PTEN, but not the G129E mutant, increased nuclear PTEN localization, CDX2, and CLDN3/CLDN4 mRNA levels in TMK-1 cells.
  • GC tumors with nuclear PTEN expression were frequently associated with an intestinal-type claudin phenotype.

Conclusions:

  • Nuclear localization of PTEN is functionally important for inducing an intestinal differentiation program in gastric cancer.
  • PTEN's role in GC may extend beyond cytoplasmic signaling to influencing cellular differentiation via nuclear localization.

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