Galectin-9 Signaling Drives Breast Cancer Invasion through Extracellular Matrix

Dharma Pally, Mallar Banerjee, Shahid Hussain, Rekha V Kumar, Alexandra Petersson, Ebba Rosendal, Ludvig Gunnarsson, Kristoffer Peterson, Hakon Leffler, Ulf J Nilsson, Ramray Bhat

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1376-1386
JournalACS Chemical Biology
Issue number6
Early online date2022 May 23
Publication statusPublished - 2022

Subject classification (UKÄ)

  • Cancer and Oncology
  • Medicinal Chemistry


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