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A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis
Biorxiv : the Preprint Server for Biology
|September 30, 2024
Summary
STAG2, a cohesin component, acts as a crucial tumor suppressor in lung cancer. Its inactivation impacts gene expression and genome structure, revealing a STAG2-PAXIP1/PAGR1 tumor-suppressive axis.
Area of Science:
- Cancer Biology
- Epigenetics
- Genomics
Background:
- The cohesin complex regulates gene expression and is crucial for genome stability.
- STAG2 is a frequently mutated cohesin subunit and a key tumor suppressor in lung cancer.
Purpose of the Study:
- To investigate the tumor-suppressive role of STAG2 and its associated factors in lung cancer.
- To elucidate the mechanisms by which STAG2 loss impacts cancer cell state and tumorigenesis.
Main Methods:
- Somatic CRISPR-Cas9 genome editing and tumor barcoding in an autochthonous KRAS-driven lung cancer model.
- Analysis of gene expression, chromatin accessibility, and 3D genome conformation.
- In vivo and in vitro studies using human lung cancer cell lines.
Main Results:
- STAG2 is uniquely tumor suppressive among cohesin components.
- PAXIP1 and PAGR1 exhibit correlated effects with STAG2 and function as tumor suppressors.
- STAG2 inactivation alters gene expression, chromatin accessibility, and 3D genome conformation.
- A STAG2-PAXIP1/PAGR1 tumor-suppressive axis was identified.
Conclusions:
- STAG2 is a critical functional suppressor of lung adenocarcinoma.
- A STAG2-PAXIP1/PAGR1 tumor-suppressive program is identified, potentially relevant across cancer types.
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