Data from: Gal-1 promotes lung cancer cell survival by enhancing PARP1/H1.2 interaction to promote DNA repair upon DNA damage response

Galectin-1 (Gal-1), a member of the galectin family, has emerged as a
regulator of tumor progression. Several studies have reported the
up-regulation of Gal-1 expression in multiple cancer cells and its
promotion on tumor proliferation. However, the mechanism by which Gal-1
promotes tumor growth remains to be thoroughly understood. In this study,
it was discovered that high expression of Gal-1 in viral cancers was
inversely correlated with the overall survival of patients. Through
constructing Gal-1-overexpressing cell lines, it was uncovered that cell
proliferation and colony formation were significantly improved. The
results of transcriptomic and proximity-labeling-based proteomic analyses
indicated that Gal-1 interacted with PARP1 and histone H1.2 in lung cancer
cells. In the case of etoposide treatment leading to DNA double-strand
breaks, Gal-1 accelerated the degradation of H1.2 by enhancing its
interaction with PARP1 and promoting its PARylation modification. It
caused the activation of downstream DNA repair pathways such as the ATM
and NBS1 signaling pathways, thus reducing apoptosis. Moreover, Gal-1
inhibitors TDG and OTX008 could restore cell sensitivity to etoposide.
This study provides new clues for the role of Gal-1 in the development of
tumors and renders suggestions for the treatment of patients with high
Gal-1 expression in the clinic.