Galectin‑9 Signaling Drives Breast Cancer Invasion through Extracellular Matrix

Aberrations
in glycan
and lectin expression and function represent
one of the earliest hallmarks of cancer. Among galectins, a conserved
family of β-galactoside-binding lectins, the role of Galectin-9
in immune–tumor interactions is well-established, although
its effect on cancer cell behavior remains unclear. In this study,
we assayed for, and observed, an association between Galectin-9 expression
and invasiveness of breast cancer cells in vitro and in vivo. Genetic perturbation and pharmacological inhibition
using novel cognate inhibitors confirmed a positive correlation between
Galectin-9 levels and the adhesion of invasive cancer cells toand
their invasion throughconstituted organomimetic extracellular
matrix microenvironments. Signaling experiments and unbiased quantitative
proteomics revealed Galectin-9 induction of Focal Adhesion Kinase
activity and S100A4 expression, respectively. FAK inhibition decreased
S100A4 mRNA levels. Our results provide crucial insights into how
elevated Galectin-9 expression potentiates the invasiveness of breast
cancer cells during early steps of invasion.