Autocrine signaling of NRP1 ligand galectin-1 elicits resistance to BRAF-targeted therapy in melanoma cells

Sabrina Rizzolio, Simona Corso, Silvia Giordano, Luca Tamagnone

Research output: Contribution to journalArticlepeer-review


Melanoma cells addicted to mutated BRAF oncogene activity can be targeted by specific kinase inhibitors until they develop resistance to therapy.We observed that the expression of Galectin-1 (Gal-1), a soluble ligand of Neuropilin-1 (NRP1), is upregulated in melanoma tumor samples and melanoma cells resistant to BRAF-targeted therapy. We then demonstrated that Gal-1 is a novel driver of resistance to BRAF inhibitors in melanoma and that its activity is linked to the concomitant upregulation of the NRP1 receptor observed in drug-resistant cells. Mechanistically, Gal-1 sustains increased expression of NRP1 and EGFR in drug-resistant melanoma cells. Moreover, consistent with its role as a NRP1 ligand, Gal-1 negatively controls p27 levels, a mechanism previously found to enable EGFR upregulation in cancer cells. Finally, the combined treatment with a Gal-1 inhibitor and a NRP1 blocking drug enabled resistant melanoma cell resensitization to BRAF-targeted therapy. In summary, we found that the activation of Galectin-1/NRP1 autocrine signaling is a new mechanism conferring independence from BRAF kinase activity to oncogene-addicted melanoma cells.

Original languageEnglish
Article number2218
Pages (from-to)1-14
Number of pages14
Issue number8
Publication statusPublished - Aug 2020


  • Autocrine signaling
  • Braf
  • Cancer therapy
  • Cell signaling
  • Egfr
  • Galectin
  • Melanoma
  • Molecular biology
  • Neuropilin
  • Oncogenic signaling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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