Gastric cancer continues to pose a significant clinical challenge worldwide. One of the primary obstacles to successful treatment is gastric cancer multidrug resistance. This resistance often leads to tumor recurrence and poor patient outcomes. Recent research has identified BATF2 as a pivotal tumor suppressor. It plays a critical role in modulating drug sensitivity in malignant cells.

Mechanism of Gastric Cancer Multidrug Resistance

The study investigated how BATF2 influences gastric cancer multidrug resistance through specific molecular pathways. Researchers utilized adriamycin and vincristine resistant cell lines for their analysis. They found significantly lower BATF2 expression in these resistant cells. Consequently, this downregulation correlates with increased cell viability and reduced apoptosis. BATF2 overexpression effectively reverses these pro-tumor changes.

Centrosome clustering is a major mechanism contributing to chromosomal instability. This process allows cancer cells to survive with extra centrosomes. Specifically, the research demonstrates that BATF2 inhibits this clustering. It reduces the expression of KIFC1, which is a known regulator of centrosome positioning. This inhibition is crucial for restoring drug sensitivity in gastric tumors.

Targeting the ATM Phosphorylation Pathway

Furthermore, the study highlights the role of ATM phosphorylation in this resistance process. BATF2 reverses resistance by suppressing the activation of ATM. Researchers validated this by using KU-60019, a specific ATM inhibitor. In addition, ATM overexpression counteracted the beneficial effects of BATF2. Therefore, the BATF2-ATM-KIFC1 axis represents a promising therapeutic target for future interventions.

In conclusion, BATF2 serves as a potential biomarker for treatment response. Targeting centrosome clustering via the ATM pathway offers a novel clinical strategy. Moreover, this approach could significantly improve the management of resistant gastric malignancies.

FAQs

How does BATF2 affect drug resistance in gastric cancer?

BATF2 reverses multidrug resistance by suppressing ATM phosphorylation and inhibiting KIFC1-mediated centrosome clustering, which promotes cancer cell apoptosis.

What is the role of ATM phosphorylation in cancer therapy?

ATM phosphorylation is a key step in the DNA damage response. In some advanced cancers, its activation helps cells survive chemotherapy and maintain chromosomal stability.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional relationship. Always consult a qualified healthcare provider for diagnosis and treatment. Refer to the latest local and national guidelines for clinical practice.

References

Yang W et al. BATF2 reverses multidrug resistance of gastric cancer cells and centrosome clustering by suppressing ATM phosphorylation. Neoplasma. 2026 Apr 30. doi: undefined. PMID: 42059142.

He et al. The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation. Nat Commun. 2021 Jan 4;12(1):20. doi: 10.1038/s41467-020-20208-x.

Huang et al. ATM Expression Predicts Veliparib and Irinotecan Sensitivity in Gastric Cancer by Mediating P53-Independent Regulation of Cell Cycle and Apoptosis. Mol Cancer Ther. 2016 Dec;15(12):3087-3096. doi: 10.1158/1535-7163.MCT-15-1002.