Related Experiment Video

Updated: Jun 5, 2025

Protein Transfection of Mouse Lung
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Protein Transfection of Mouse Lung

Published on: May 15, 2013

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A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis

Emily L Ashkin1, Yuning J Tang2, Haiqing Xu3

  • 1Cancer Biology Program, Stanford University School of Medicine , Stanford, CA, USA.

The Journal of Experimental Medicine
|December 9, 2024
PubMed

Insights

STAG2 is a key tumor suppressor in lung cancer. Its inactivation affects gene expression and genome structure, revealing a STAG2-PAXIP1/PAGR1 tumor-suppressive axis.

Area of Science:

  • Genetics
  • Cancer Biology
  • Epigenetics

Background:

  • The cohesin complex regulates gene expression.
  • STAG2 mutations are frequent in cancers, notably as a lung cancer tumor suppressor.

Purpose of the Study:

  • Investigate STAG2's unique tumor-suppressive role in lung cancer.
  • Identify cohesin-related tumor suppressors and their mechanisms.

Main Methods:

  • Somatic CRISPR-Cas9 genome editing.
  • Tumor barcoding in an oncogenic KRAS-driven lung cancer model.
  • Analysis of gene expression, chromatin accessibility, and 3D genome conformation.

Main Results:

  • STAG2 is uniquely tumor-suppressive among cohesin components.
  • PAXIP1 and PAGR1 exhibit correlated effects with STAG2 and act as in vivo tumor suppressors.
  • STAG2 inactivation alters gene expression, chromatin accessibility, and genome conformation.
  • Similarities between STAG2- and PAXIP1-deficient cells link STAG2-cohesin to PAXIP1/PAGR1.

Conclusions:

  • A STAG2-PAXIP1/PAGR1 tumor-suppressive axis is identified.
  • Novel STAG2-cohesin mechanisms, including PAXIP1-dependent and -independent pathways, in lung tumor suppression are uncovered.

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