WCLC 2025 - Posters & ePosters-P2.02.17 GNAZ as a Tumor Suppressor Marker Inhibits Tumor Development Through Interaction With the KIF11 Protein

P2.02.17 GNAZ as a Tumor Suppressor Marker Inhibits Tumor Development Through Interaction With the KIF11 Protein

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This study investigates the role of GNAZ in lung adenocarcinoma (LUAD) and its interaction with the third-generation EGFR tyrosine kinase inhibitor (TKI) Osimertinib, a key treatment for patients with specific EGFR mutations (L858R and T790M). Despite advancements, lung cancer remains the leading cause of cancer-related deaths globally, highlighting the need for improved therapies, especially for those resistant to earlier-generation TKIs.<br /><br />Using a combination of in vitro assays—including colony formation, Transwell migration, flow cytometry—and in vivo xenograft models in nude mice, researchers demonstrated that GNAZ acts as a tumor suppressor in LUAD. GNAZ expression was found to inhibit tumor growth and enhance the therapeutic response to Osimertinib.<br /><br />Mass spectrometry analysis identified proteins interacting with GNAZ and showed that GNAZ affects post-translational modifications of KIF11, a motor protein involved in cell division. This modulation by GNAZ helps reverse epithelial–mesenchymal transition (EMT), a process pivotal in tumor progression and metastasis.<br /><br />The findings suggest that GNAZ enhances Osimertinib efficacy by disrupting EMT, offering a novel mechanism to overcome drug resistance in LUAD. Given the limited options for Osimertinib-resistant cancers and the severe side effects associated with other treatments like Tepotinib, targeting GNAZ or its downstream pathways could provide a critical therapeutic strategy.<br /><br />In conclusion, this research highlights GNAZ as a potential tumor suppressor and synergistic agent with Osimertinib in lung cancer treatment, offering new insights for addressing resistance and improving patient outcomes.

Asset Subtitle

Shuning Kong

Meta Tag

Speaker Shuning Kong

Topic Tumor Biology – Preclinical Biology

Keywords

GNAZ

lung adenocarcinoma

LUAD

Osimertinib

EGFR mutations

tyrosine kinase inhibitor

tumor suppressor

epithelial–mesenchymal transition

KIF11

drug resistance