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Updated: Jun 11, 2025

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
10:21

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

Published on: September 20, 2024

393

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis

Emily L Ashkin, Yuning J Tang, Haiqing Xu

    Biorxiv : the Preprint Server for Biology
    |September 30, 2024
    PubMed

    Insights

    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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