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The nuclear transport receptor Importin-11 is a tumor suppressor that maintains PTEN protein

Muhan Chen1, Dawid G Nowak1, Navneet Narula2,3

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.

The Journal of Cell Biology
|February 15, 2017
PubMed

Insights

Importin-11 (Ipo11) transports PTEN, preventing its degradation. Loss of Ipo11 leads to PTEN loss, promoting lung adenocarcinoma and prostate cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • PTEN protein is crucial for tumor suppression.
  • Mechanisms driving PTEN degradation in cancer are not fully understood.

Purpose of the Study:

  • Investigate the role of Importin-11 (Ipo11) in PTEN regulation.
  • Determine the mechanism by which Ipo11 affects PTEN stability and function.
  • Evaluate IPO11 as a potential tumor suppressor and prognostic marker.

Main Methods:

  • In vitro and in vivo gene targeting.
  • Analysis of protein levels and cellular localization.
  • Correlation studies in human lung and prostate cancer tissues.

Main Results:

  • Ipo11 acts as a PTEN transport receptor, protecting it from degradation machinery.
  • UBE2E1, an Ipo11 cargo, is a rate-limiting factor for PTEN degradation.
  • Ipo11 loss causes PTEN degradation, leading to lung adenocarcinoma and prostate neoplasia in mice.
  • Loss of IPO11 correlates with decreased PTEN protein in human lung tumors.
  • IPO11 status predicts recurrence and metastasis in prostate cancer patients.

Conclusions:

  • IPO11 is a tumor suppressor locus critical for maintaining PTEN protein levels.
  • IPO11 function is essential in cancers with intact PTEN alleles.
  • IPO11 is a potential prognostic biomarker for cancer recurrence and metastasis.

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