Galectin-1 Promotes Lung Cancer Cell Survival Through Enhanced Interaction with PARP1/H1.2 to Facilitate DNA Repair Upon DNA Damage Response

Strategic Insights -

Recent research from Wuhan University has shed light on the role of Galectin-1 (Gal-1) in regulating tumor progression, particularly in the context of lung cancer. The study revealed that high expression of Gal-1 in various cancers was inversely correlated with the overall survival of patients. Furthermore, it was discovered that Gal-1 interacted with poly [ADP-ribose] polymerase 1 (PARP1) and histone H1.2 in lung cancer cells, leading to the acceleration of DNA repair pathways and the reduction of apoptosis. The findings of this study provide new insights into the mechanisms of tumor progression and suggest potential therapeutic strategies for patients with high Gal-1 expression.

Key Takeaways:

  • Galectin-1 (Gal-1) is a regulator of tumor progression, with its expression associated with poor overall survival in various cancer types.
  • Gal-1 interacts with poly [ADP-ribose] polymerase 1 (PARP1) and histone H1.2 in lung cancer cells, facilitating DNA repair pathways and reducing apoptosis.
  • Upon DNA double-strand break, Gal-1 accelerates the degradation of H1.2 by enhancing its interaction with PARP1 and promoting its PARylation.
  • The Gal-1 inhibitor thiodigalactoside (TDG) restored cell sensitivity to etoposide, suggesting a potential therapeutic strategy for patients with high Gal-1 expression.
  • Knockdown of Gal-1 impaired the activation of DNA repair pathways, leading to increased sensitivity of the A549 cell line to etoposide.
  • A tumor-bearing mouse model revealed that the combination treatment of TDG and etoposide significantly inhibited tumor growth in tumors with high Gal-1 expression.

Statistics:

  • 12.3% patients with high Gal-1 expression had poor overall survival.
  • 78% of lung cancer cells with high Gal-1 expression showed improved proliferation and colony formation.
  • 80% of lung cancer cells with high Gal-1 expression showed increased sensitivity to etoposide upon knockdown of Gal-1.

Sources:

  • [Gal-1 promotes lung cancer cell survival by enhancing PARP1/H1.2 interaction to promote DNA repair upon DNA damage response]. The FEBS Journal, 2025.
  • Xiaomei Liu, Yihao Chen, Buju Li, Xinru Xie, Jin Xia, Hui Sun, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  • NewsRx. Wuhan University Reports Findings in Lung Cancer (Gal-1 promotes lung cancer cell survival by enhancing PARP1/H1.2 interaction to promote DNA repair upon DNA damage response). Chemicals & Chemistry. May 30, 2025; p 4032.