Galectin-3 contributes to melanoma growth and metastasis via regulation of NFAT1 and autotaxin

Cancer Res. 2012 Nov 15;72(22):5757-66. doi: 10.1158/0008-5472.CAN-12-2424. Epub 2012 Sep 17.


Melanoma is the deadliest form of skin cancer in which patients with metastatic disease have a 5-year survival rate of less than 10%. Recently, the overexpression of a β-galactoside binding protein, galectin-3 (LGALS3), has been correlated with metastatic melanoma in patients. We have previously shown that silencing galectin-3 in metastatic melanoma cells reduces tumor growth and metastasis. Gene expression profiling identified the protumorigenic gene autotaxin (ENPP2) to be downregulated after silencing galectin-3. Here we report that galectin-3 regulates autotaxin expression at the transcriptional level by modulating the expression of the transcription factor NFAT1 (NFATC2). Silencing galectin-3 reduced NFAT1 protein expression, which resulted in decreased autotaxin expression and activity. Reexpression of autotaxin in galectin-3 silenced melanoma cells rescues angiogenesis, tumor growth, and metastasis in vivo. Silencing NFAT1 expression in metastatic melanoma cells inhibited tumor growth and metastatic capabilities in vivo. Our data elucidate a previously unidentified mechanism by which galectin-3 regulates autotaxin and assign a novel role for NFAT1 during melanoma progression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Galectin 3 / biosynthesis
  • Galectin 3 / deficiency*
  • Galectin 3 / genetics
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Melanoma / blood supply
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • NFATC Transcription Factors / biosynthesis*
  • NFATC Transcription Factors / genetics
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Phosphoric Diester Hydrolases / biosynthesis*
  • Phosphoric Diester Hydrolases / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Transfection


  • Galectin 3
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase